CT Coronary Angiography with 100kV tube voltage and a low noise reconstruction filter in non-obese patients: evaluation of radiation dose and diagnostic quality of 2D and 3D image reconstructions using open source software (OsiriX)

INTRODUCTION AND PURPOSE. Computed tomography coronary angiography (CTCA) has seen a dramatic evolution in the last decade owing to the availability of multislice CT scanners with 64 detector rows and beyond. However, this evolution has been paralleled by an increase in radiation dose to patients, that can reach extremely high levels (>20mSv) when retrospective ECG-gating techniques are used. On CT angiography, reduction of tube voltage allows to cut radiation dose with improved contrast resolution due to the lower energy of the X-ray beam and increased photoelectric effect. Our purpose is twofold: 1) to evaluate the radiation dose of CTCA studies carried out using a tube voltage of 100kV and a low noise reconstruction filter, compared with a conventional tube voltage of 120kV and a standard reconstruction kernel; 2) to assess the impact of the 100kV acquisition technique on the diagnostic quality of 2D and 3D image reconstructions performed with open source software (OsiriX). MATERIALS AND METHODS. Fifty-one non-obese patients underwent CTCA on a 64-row CT scanner. Out of them, 28 were imaged using a tube voltage of 100kV and a low noise reconstruction filter, while in the remaining 23 patients a tube voltage of 120kV and a standard reconstruction kernel were selected. All CTCA datasets were exported via PACS to a Macintosh™ computer (iMac™) running OsiriX 4.0 (64-bit version), and Maximum Intensity Projection (MIP), Curved Planar Reformation (CPR), and Volume Rendering (VR) views of each coronary artery were generated using a dedicated plug-in (CMIV CTA; Linköping University, Sweden). Diagnostic quality of MIP, CPR, and VR reconstructions was assessed visually by two radiologists with experience in cardiac CT using a three-point score (1=poor, 2=good, 3=excellent). Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), intravascular CT density, and effective dose for each group were also calculated. RESULTS. Image quality of VR views was significantly better with the 100kV than with the 120kV protocol (2.77±0.43 vs 2.21±0.85, p=0.0332), while that of MIP and CPR reconstructions was comparable (2.59±0.50 vs 2.32±0.75, p=0.3271, and 2.68±0.48 vs 2.32±0.67, p=0.1118, respectively). SNR and CNR were comparable between the two protocols (16.42±4.64 vs 14.78±2.57, p=0.2502, and 13.43±3.77 vs 12.08±2.10, p=0.2486, respectively), but in the 100kV group aortic root density was higher (655.9±127.2 HU vs 517.2±69.7 HU, p=0.0016) and correlated with VR image quality (rs=0.5409, p=0.0025). Effective dose was significantly lower with the 100kV than with the 120kV protocol (7.43±2.69 mSv vs 18.83±3.60 mSv, p<0.0001). CONCLUSIONS. Compared with a standard tube voltage of 120kV, usage of 100kV and a low noise filter leads to a significant reduction of radiation dose with equivalent and higher diagnostic quality of 2D and 3D reconstructions, respectively in non-obese patients

The Nefarious Nexus of Noncoding RNAs in Cancer

The past decade has witnessed enormous progress, which has seen the noncoding RNAs (ncRNAs) turn from the so called dark matter RNA to critical functional molecules, influencing most physiological processes in development and disease contexts. Many ncRNAs interact with each other and are part of networks that influence the cell transcriptome and proteome and consequently the outcome of biological processes. The regulatory circuits controlled by ncRNAs have become increasingly more relevant in cancer. Further understanding of these complex network interactions and how ncRNAs are regulated, is paving the way for the identification of better therapeutic strategies in cancer

A System to Improve Port Navigation Safety and Its Use in Italian Harbours

This article describes research aimed at developing a system able to support local authorities and port communities in optimizing port navigation, avoiding or managing critical situations induced by sea-level variations in harbours and minimizing environmental damages and economic losses. In the Mediterranean basin, sea-level changes are mostly due to astronomical tides, related to the gravitational attraction between Earth, Moon and Sun. Nevertheless, sea-level variations are also influenced by meteorological tides, which are geodetic adjustments of sea surface due to atmospheric pressure variations above a water basin. So, starting from monitoring or forecasting environmental parameters in harbours, the system updates port bathymetric maps based on sea-level variations (acquired in the past, measured in real-time, or expected in the future) and detects hazardous areas for a certain ship moving inside a port at a given moment, by means of the implementation of "virtual traffic lights". The system was tested on some real situations, including the analysis of maritime accidents (stranding of ships), providing satisfactory results by correctly signalling potentially dangerous areas variable over time. The architecture of the system and results achieved using it in the ports of Livorno and Bari, in Italy, are herewith described

Cytotoxic drugs activate KSHV lytic cycle in latently infected PEL cells by inducing a moderate ROS increase controlled by HSF1, NRF2 and p62/SQSTM1

Previous studies have indicated that cytotoxic treatments may induce or not activate viral lytic cycle activation in cancer cells latently infected by Kaposi’s sarcoma-associated herpesvirus (KSHV). To investigate the molecular mechanisms responsible for such an effect, we compared two cytotoxic treatments able to induce the viral lytic cycle, named 12-O-tetradecanoylphorbol 13-acetate (TPA) (T) in combination with sodium butyrate (B) and bortezomib (BZ), with two cytotoxic treatments that did not activate this process, named metformin (MET) and quercetin (Q). Our results indicated that TB and bortezomib increased levels of oxygen reactive species (ROS) while metformin and quercetin reduced them. The finding that N-acetylcysteine (NAC), a reactive oxigen species (ROS) scavenger, counteracted K-bZIP expression induced by TB or bortezomib, confirmed that an ROS increase played a role in KSHV lytic cycle activation. Moreover, we found that TB and bortezomib up-regulated p62/Sequestosome1(p62/SQSTM1) protein, while metformin and quercetin down-regulated it. p62/SQSTM1 silencing or the inhibition of NF-E2-related factor 2 (NRF2) or Heat Shock Factor 1 (HSF1), that mediate p62/SQSTM1 transcription, also reduced KSHV lytic antigen expression induced by TB or bortezomib. Interestingly, such combination treatments further increased intracellular ROS and cytotoxicity induced by the single TB or bortezomib treatment, suggesting that NRF2, HSF1 and p62/SQSTM1 keep the ROS level under control, allowing primary effusion lymphoma (PEL) cells to continue to survive and KSHV to replicate

Targeting of Prosurvival Pathways as Therapeutic Approaches against Primary Effusion Lymphomas: Past, Present, and Future

Constitutively activated prosurvival pathways render cancer cells addicted to their effects. Consequently they turn out to be the Achilles’ heels whose inhibition can be exploited in anticancer therapy. Primary effusion lymphomas (PELs) are very aggressive non-Hodgkin’s B cell lymphomas, whose pathogenesis is strictly linked to Kaposi’s sarcoma herpesvirus (KSHV) infection. Here we summarized previous studies from our and other laboratories exploring the cytotoxic effect of drugs inhibiting the main prosurvival pathways activated in PEL cells. Moreover, the immunogenicity of cell death, in terms of dendritic cell (DC) activation and their potential side effect on DCs, is discussed

Apigenin, by activating p53 and inhibiting STAT3, modulates the balance between pro-apoptotic and pro-survival pathways to induce PEL cell death

BACKGROUND: Apigenin is a flavonoid widely distributed in plant kingdom that exerts cytotoxic effects against a variety of solid and haematological cancers. In this study, we investigated the effect of apigenin against primary effusion lymphoma (PEL), a KSHV-associated B cell lymphoma characterized by a very aggressive behavior, displaying constitutive activation of STAT3 as well as of other oncogenic pathways and harboring wtp53. METHODS: Cell death was assessed by trypan blue exclusion assay, FACS analysis as well as by biochemical studies. The latter were also utilized to detect the occurrence of autophagy and the molecular mechanisms leading to the activation of both processes by apigenin. FACS analysis was used to measure the intracellular ROS utilizing DCFDA. RESULTS: We show that apigenin induced PEL cell death and autophagy along with reduction of intracellular ROS. Mechanistically, apigenin activated p53 that induced catalase, a ROS scavenger enzyme, and inhibited STAT3, the most important pro-survival pathway in PEL, as assessed by p53 silencing. On the other hand, STAT3 inhibition by apigenin resulted in p53 activation, since STAT3 negatively influences p53 activity, highlighting a regulatory loop between these two pathways that modulates PEL cell death/survival. CONCLUSION: The findings of this study demonstrate that apigenin may modulate pro-apoptotic and pro-survival pathways representing a valid therapeutic strategy against PEL

DENDRITIC CELL DIFFERENTIATION BLOCKED BY PRIMARY EFFUSION LYMPHOMA-RELEASED FACTORS IS PARTIALLY RESTORED BY INHIBITION OF P38 MAPK

To better understand the molecular mechanisms underlying the dendritic cell (DC) defects in cancer, we analyzed which signaling pathway is implicated in the abnormal monocyte differentiation into DC determined by the presence of Primary effusion lymphoma (PEL) released factors. Our results indicate that the DC, obtained in this condition, together with phenotypic abnormalities and reduced allostimulatory function, showed hyperphosphorylation of signal transducer and activator of transcription 3 (STAT3) and p38 mitogen-activated protein kinase (MAPK) molecules, in comparison to the DC differentiated in the absence of PEL-released factors. The inhibition of p38 MAPK but not of STAT3 phosphorylation, with specific inhibitors, was able to revert the effect of the PEL-released factors on the DC phenotype. This study suggests that p38 MAPK signaling pathway is an important contributor to the abnormal differentiation of DC in PEL

HMGB1-Induced Cross Talk between PTEN and miRs 221/222 in Thyroid Cancer

High mobility group box 1 (HMGB1) is an ubiquitous protein that plays different roles in the nucleus, cytoplasm and extra-cellular space. It is an important DAMP molecule that allows communication between damaged or tumor cells and the immune system. Tumor cells exploit HMGB1’s ability to activate intracellular pathways that lead to cell growth and migration. Papillary thyroid cancer is a well differentiated tumor and is often used to study relationships between cells and the inflammatory microenvironment as the latter is characterized by high levels of inflammatory cells and cytokines. Anaplastic thyroid cancer is one of the most lethal human cancers in which many microRNAs and tumor suppressor genes are de-regulated. Up-regulation of microRNAs 221 and 222 has been shown to induce the malignant phenotype in many human cancers via inhibition of PTEN expression. In this study we suggest that extracellular HMGB1 interaction with RAGE enhances expression of oncogenic cluster miR221/222 that in turn inhibits tumor suppressor gene PTEN in two cell lines derived from human thyroid anaplastic and papillary cancers. The newly identified pathway HMGB1/RAGE/miR 221/222 may represent an effective way of tumor escape from immune surveillance that could be used to develop new therapeutic strategies against anaplastic tumors

imaging biomarkers in upper gastrointestinal cancers

In parallel with the increasingly widespread availability of high performance imaging platforms and recent progresses in pathobiological characterisation and treatment of gastrointestinal malignancies, imaging biomarkers have become a major research topic due to their potential to provide additional quantitative information to conventional imaging modalities that can improve accuracy at staging and follow-up, predict outcome, and guide treatment planning in an individualised manner. The aim of this review is to briefly examine the status of current knowledge about imaging biomarkers in the field of upper gastrointestinal cancers, highlighting their potential applications and future perspectives in patient management from diagnosis onwards

The activation of KSHV lytic cycle blocks autophagy in PEL cells

This study confirms that autophagy is activated concomitantly with KSHV lytic cycle induction, and that autophagy inhibition by BECN1 knockdown reduces viral lytic gene expression. In addition, we extend previous observations and show that autophagy is blocked at late steps, during viral replication. This is indicated by the lack of colocalization of autophagosomes and lysosomes and by the LC3-II level that does not increase in the presence of bafilomycin A1 in primary effusion lymphoma (PEL) cells induced to enter the lytic cycle, either by TPA/sodium butyrate (BC3 and BCBL1) or by doxycycline (TRExBCBL1-Rta). The autophagic block correlates with the downregulation of RAB7, whose silencing with specific siRNA results in an autophagic block in the same cells. Finally, by electron microscopy analysis, we observed viral particles inside autophagic vesicles in the cytoplasm of PEL cells undergoing viral replication, suggesting that they may be involved in viral transpor