Viruses, Vol. 8, Pages 20: Features of the Antitumor Effect of Vaccinia Virus Lister Strain

Oncolytic abilities of vaccinia virus (VACV) served as a basis for the development of various recombinants for treating cancer; however, "natural" oncolytic properties of the virus are not examined in detail. Our study was conducted to know how the genetically unmodified L-IVP strain of VACV produces its antitumor effect. Human A431 carcinoma xenografts in nude mice and murine Ehrlich carcinoma in C57Bl mice were used as targets for VACV, which was injected intratumorally. A set of virological methods, immunohistochemistry, light and electron microscopy was used in the study. We found that in mice bearing A431 carcinoma, the L-IVP strain was observed in visceral organs within two weeks, but rapidly disappeared from the blood. The L-IVP strain caused decrease of sizes in both tumors, however, in different ways. Direct cell destruction by replicating virus plays a main role in regression of A431 carcinoma xenografts, while in Ehrlich carcinoma, which poorly supported VACV replication, the virus induced decrease of mitoses by pushing tumor cells into S-phase of cell cycle. Our study showed that genetically unmodified VACV possesses at least two mechanisms of antitumor effect: direct destruction of tumor cells and suppression of mitoses in tumor cells.

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Improved Mitochondrial and Methylglyoxal-Related Metabolisms Support Hyperproliferation Induced by 50 Hz Magnet ic Field in Neuroblastoma Cells

Abstract

Extremely low frequency magnetic fields (ELF-MF) are common environmental agents that are suspected to promote later stages of tumorigenesis, especially in brain-derived malignancies. Even though ELF magnetic fields have been previously linked to increased proliferation in neuroblastoma cells, no previous work has studied whether ELF-MF exposure may change key biomolecular features, such as anti-glycative defence and energy re-programming, both of which are currently considered as crucial factors involved in the phenotype and progression of many malignancies.

Our study investigated whether the hyperproliferation that is induced in SH-SY5Y human neuroblastoma cells by a 50 Hz, 1 mT ELF magnetic field is supported by an improved defense towards methylglyoxal (MG), which is an endogenous cancer-static and glycating α-oxoaldehyde, and by rewiring of energy metabolism.

Our findings show that not only the ELF magnetic field interfered with the biology of neuron-derived malignant cells, by de-differentiating further the cellular phenotype and by increasing the proliferative activity, but also triggered cytoprotective mechanisms through the enhancement of the defense against MG, along with a more efficient management of metabolic energy, presumably to support the rapid cell outgrowth. Intriguingly, we also revealed that the MF-induced bioeffects took place after an initial imbalance of the cellular homeostasis, which most likely created a transient unstable milieu. The biochemical pathways and molecular targets revealed in this research could be exploited for future approaches aimed at limiting or suppressing the deleterious effects of ELF magnetic fields. This article is protected by copyright. All rights reserved

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The relationship between EMT, CD44high/EGFRlow phenotype, and treatment response in head and neck cancer cell lines

Background

Head and neck squamous cell carcinoma (HNSCC) tumors are often therapy resistant and may originate from cancer stem cells or tumor cells with an epithelial-to-mesenchymal transition (EMT) phenotype. The aim of this study was to characterize HNSCC cell lines with regard to EMT profile and to investigate the influence of EMT on the response to treatment.

Methods

mRNA expression of the EMT-associated genes CDH1 (E-cadherin), CDH2 (N-cadherin), FOXC2, TWIST1, VIM (vimentin), and FN1 (fibronectin) was determined using quantitative real-time PCR. Cell morphology and migration were investigated by phase-contrast microscopy and Boyden chamber assay, respectively. The cell surface expression of CD44 and epidermal growth factor receptor (EGFR) was examined by flow cytometry. The response to radiotherapy, cetuximab, and dasatinib was assessed by crystal violet staining.

Results

A total of 25 cell lines investigated differed greatly with regard to EMT phenotype. Cell lines with an EMT expression profile showed a mesenchymal morphology and a high migratory capacity. In addition, they exhibited a high cell surface expression of CD44 and a low expression of EGFR, a pattern previously associated with stemness. When the EMT inducer transforming growth factor-β (TGF-β) was added to non-EMT cells, changes in treatment responses were observed. Moreover, the expression of TWIST1 was found to correlate with radioresistance.

Conclusions

The data presented in this report suggest that EMT is associated with a CD44high/EGFRlow phenotype and possibly negative impact on radiotherapy response in HNSCC cell lines.

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Interaction of stromal and microvascular components in keratocystic odontogenic tumors

Objective

Little is known about the interaction of stromal components in odontogenic tumors. Thus, the aim of this study was to investigate mast cells (MCs), myofibroblasts, macrophages, and their possible association with angiogenesis and lymphangiogenesis in keratocystic odontogenic tumors (KCOTs).

Material and Methods

Thirty cases of KCOTs were included and analyzed by immunohistochemistry for mast cell tryptase, α-SMA, CD34, CD163, and D240. For comparative purpose, 15 radicular cysts (CRs) and 7 pericoronal follicles (PFs) were included.

Results

There was an increase in MCs for RCs and this difference was significant when they were compared to KCOTS and PFs. A significant increase in the density of MFs was observed for KCOTs when compared to RCs and PFs (P = 0.00). No significant difference in CD163-positive macrophages (P = 0.084) and CD34-positive vessels (P = 0.244) densities was observed between KCOTs, RCs, and PFs, although KCOTs showed a higher density of all proteins. Significant difference in lymphatic vessel density was observed for KCOTs when compared to RCs and PFs (P = 0.00). Positive correlation was observed between mast cell tryptase and CD34 in KCOTs (P = 0.025).

Conclusions

A significant interaction between the MC population and CD34-positive vessels in KCOTs supported the hypothesis that MCs and blood vessels contribute to the stromal scaffold of KCOT.

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Viruses, Vol. 8, Pages 18: Defining the Enterovirus Diversity Landscape of a Fecal Sample: A Methodological Challenge?

Enteroviruses are a group of over 250 naked icosahedral virus serotypes that have been associated with clinical conditions that range from intrauterine enterovirus transmission withfataloutcome through encephalitis and meningitis, to paralysis. Classically, enterovirus detection was done by assaying for the development of the classic enterovirus-specific cytopathic effect in cell culture. Subsequently, the isolates were historically identified by a neutralization assay. More recently, identification has been done by reverse transcriptase-polymerase chain reaction (RT-PCR). However, in recent times, there is a move towards direct detection and identification of enteroviruses from clinical samples using the cell culture-independent RT semi-nested PCR (RT-snPCR) assay. This RT-snPCR procedure amplifies the VP1 gene, which is then sequenced and used for identification. However, while cell culture-based strategies tend to show a preponderance of certain enterovirus species depending on the cell lines included in the isolation protocol, the RT-snPCR strategies tilt in a different direction. Consequently, it is becoming apparent that the diversity observed in certain enterovirus species, e.g., enterovirus species B(EV-B), might not be because they are the most evolutionarily successful. Rather, it might stem from cell line-specific bias accumulated over several years of use of the cell culture-dependent isolation protocols. Furthermore, it might also be a reflection of the impact of the relative genome concentration on the result of pan-enterovirus VP1 RT-snPCR screens used during the identification of cell culture isolates. This review highlights the impact of these two processes on the current diversity landscape of enteroviruses and the need to re-assess enterovirus detection and identification algorithms in a bid to better balance our understanding of the enterovirus diversity landscape.

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A 5-year comparison of emergency department visits by homeless and non-homeless patients

Publication date: Available online 11 January 2016
Source:The American Journal of Emergency Medicine
Author(s): Allison Tadros, Shelley M. Layman, Marissa Pantaleone Brewer, Stephen M. Davis
BackgroundA 2005 study examined Emergency Department (ED) utilization by homeless patients in the United States. Within the following five years, unemployment increased by 5%.ObjectiveTo analyze changes in ED utilization between 2005 and 2010 by homeless patients and compare to non-homeless visits.MethodsData from the 2010 National Hospital Ambulatory Medical Care Survey was evaluated.ResultsApproximately 679,854 visits were made by homeless patients, the majority of which were made by males (72.3%) and patients between the ages of 45–64 (50.5%). Homeless patients were twice as likely to be uninsured. ED visits by homeless patients had increased by 44% during the 5year period. Arrival to the ED by ambulance increased by 14% between the study years and homeless patients were less likely to be admitted.ConclusionThe number of visits by homeless patients in the ED increased proportionally to an overall increase in ED visits between 2005 and 2010.

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Melatonin’s protective effect on the salivary gland against ionized radiation damage in rats

Objectives

The aim of this study was to examine the effects of melatonin on ionized radiation-induced salivary gland damage using an experimental model.

Materials and Methods

Thirty-two rats were randomized into four groups: (i) the control group (C, n = 8) that received intraperitoneal (i.p.) 0.9% NaCl; (ii) the melatonin group (M, n = 8) that received i.p. 5 mg/kg melatonin; (iii) the radiotherapy group (RT, n = 8) that underwent irradiation; (iv) the melatonin plus radiotherapy group (M+RT, n = 8) that received i.p. 5 mg/kg of melatonin, followed by irradiation 30 min later; and (v) the radiotherapy plus melatonin group (RT+M, n = 8) that received irradiation followed by i.p. 5 mg/kg of melatonin 30 min later. The medications and irradiation were administered for 5 days and the salivary glands of the rats were excised 10 days later; the histopathological changes in the salivary glands were assessed and biochemical analyses were conducted (tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI)).

Results

Regardless of whether melatonin was administered before or after radiotherapy, melatonin decreased the radiation-induced parotid and submandibular histological damage. In addition, regardless of whether administration occurred before or after radiotherapy, melatonin decreased oxidative stress markers, such as MDA, TOS, and OSI. On the contrary, levels of antioxidative markers, such as CAT and GPx, were increased by melatonin.

Conclusions

Melatonin may have a significant protective effect on salivary gland damage secondary to ionizing radiation.

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