Anti-stromal treatment together with chemotherapy targets multiple signalling pathways in pancreatic adenocarcinoma.

Stromal targeting for pancreatic ductal adenocarcinoma (PDAC) is rapidly becoming an attractive option, due to the lack of efficacy of standard chemotherapy and increased knowledge about PDAC stroma. We postulated that the addition of stromal therapy may enhance the anti-tumour efficacy of chemotherapy. Gemcitabine and all-trans retinoic acid (ATRA) were combined in a clinically applicable regimen, to target cancer cells and pancreatic stellate cells (PSCs) respectively, in 3D organotypic culture models and genetically engineered mice (LSL-Kras(G12D) (/+) ;LSL-Trp53(R172H) (/+) ;Pdx-1-Cre: KPC mice) representing the spectrum of PDAC.

TIRF high-content assay development for the evaluation of drug efficacy of chemotherapeutic agents against EGFR-/HER2-positive breast cancer cell lines.

Elevated expression of epidermal growth factor receptor (EGFR) is reported to be associated with poor prognosis in breast cancer. EGFR subtype identification plays a crucial role in deciding the drug combination to treat the cancer patients. Conventional application of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) produces more discordance results in EGFR subtype identification of cancer specimens.

Evaluation of general-purpose collimators against high-resolution collimators with resolution recovery with a view to reducing radiation dose in myocardial perfusion SPECT: A preliminary phantom study.

Background: There is a growing focus on reducing radiation dose to patients undergoing myocardial perfusion imaging. This preliminary phantom study aims to evaluate the use of general-purpose collimators with resolution recovery (RR) to allow a reduction in patient radiation dose.

Methods: Images of a cardiac torso phantom with inferior and anterior wall defects were acquired on a GE Infinia and Siemens Symbia T6 using both high-resolution and general-purpose collimators.

Quantitative relationship between coronary artery calcium and myocardial blood flow by hybrid rubidium-82 PET/CT imaging in patients with suspected coronary artery disease.

Background: We assessed the relationship between coronary artery calcium (CAC) score, myocardial blood flow (MBF) and coronary flow reserve (CFR) in patients undergoing hybrid Rb positron emission tomography (PET)/computed tomography (CT) imaging for suspected CAD. We also evaluated if CAC score is able to predict a reduced CFR independently from conventional coronary risk factors.

Methods: A total of 637 (mean age 58 ± 13 years) consecutive patients were studied.

Crosstalk-eliminated quantitative determination of aflatoxin B1-induced hepatocellular cancer stem cells based on concurrent monitoring of CD133, CD44, and aldehyde dehydrogenase1.

Cancer stem cells (CSCs), known as tumor initiating cells, have become a critically important issue for cancer therapy. Although much research has demonstrated the induction of hepato cellular carcinoma by aflatoxin B1, the formation of hepatocellular CSCs and their quantitative determination is hardly reported. In this work, it was found that hepatocellular CSCs were produced from HepG2 cells by aflatoxin B1-induced mutation, and their amount was quantitatively determined using crosstalk-eliminated multicolor cellular imaging based on quantum dot (Qdot) nanoprobes and an acousto-optical tunable filter (AOTF).

Placenta growth factor augments airway hyperresponsiveness via leukotrienes and IL-13.

Airway hyperresponsiveness (AHR) affects 55%-77% of children with sickle cell disease (SCD) and occurs even in the absence of asthma. While asthma increases SCD morbidity and mortality, the mechanisms underlying the high AHR prevalence in a hemoglobinopathy remain unknown. We hypothesized that placenta growth factor (PlGF), an erythroblast-secreted factor that is elevated in SCD, mediates AHR.

Radionuclide Imaging of Cardiovascular Infection.

Owing to expanding clinical indications, cardiac implantable electronic devices (CIEDs) are being increasingly used. Despite improved surgical techniques and the use of prophylactic antimicrobial therapy, the rate of CIED-related infection is also increasing. Infection is a potentially serious complication, with clinical manifestations ranging from surgical site infection and local symptoms in the region of the generator pocket to fulminant endocarditis.

The effect of electrode size and surface heterogeneity on electrochemical properties of ultrananocrystalline diamond microelectrode.

We report here the effect of electrode size on electrochemical properties of boron-doped ultrananocrystalline diamond (UNCD) microelectrodes using electrochemical impedance spectroscopy (EIS). By reducing microelectrode size from 250-μm to 10-μm diameter (), the shape of impedance spectra changes from linear line to two-arcs. The fitting of experimental data to electrochemical circuit model suggests that each arc likely corresponds to UNCD grains and grain boundary phases.

Genetic diminution of circulating prothrombin ameliorates multiorgan pathologies in sickle cell disease mice.

Sickle cell disease (SCD) results in vascular occlusions, chronic hemolytic anemia, and cumulative organ damage. A conspicuous feature of SCD is chronic inflammation and coagulation system activation. Thrombin (factor IIa [FIIa]) is both a central protease in hemostasis and a key modifier of inflammatory processes.

Limited utility of inflammatory markers in the early detection of postoperative inflammatory complications after pancreatic resection: Cohort study and meta-analyses.

Purpose: To examine the diagnostic accuracy of systemic inflammatory markers in early prediction of inflammatory postoperative complications (IPC) and clinically-relevant pancreatic fistula (PF).

Methods: Preoperative and postoperative [until postoperative day (POD) 4)] measurements of hemoglobin, white blood cell counts (WBC), neutrophil/lymphocyte ratio (NLR) and C-reactive protein (CRP) were correlated with IPC and PF. Meta-analyses of biochemical predictors were performed.

Individuals with impaired glucose tolerance demonstrate normal cardiac sympathetic innervation using I-123 mIBG scintigraphy.

Background: Impaired glucose tolerance (IGT) is associated with an increased risk of type 2 diabetes (T2DM) and cardiovascular disease. Some but not all studies have reported cardiac autonomic dysfunction in subjects with IGT and there is only one direct study of cardiac innervation in subjects with IGT. The purpose of this study was to assess global and regional cardiac sympathetic innervation and cardiac autonomic function in individuals with IGT.

Early diagnosis of cardiac implantable electronic device generator pocket infection using ¹⁸F-FDG-PET/CT.

Aims: To examine the utility of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the early diagnosis of cardiac implantable electronic device (CIED) generator pocket infection.

Methods And Results: A total of 86 patients with CIEDs were evaluated with (18)F-FDG PET/CT imaging: 46 with suspected generator pocket infection and 40 without any history of infection. (18)F-FDG activity in the region of the generator pocket was expressed as a semi-quantitative ratio (SQR)-defined as the maximum count rate around the CIED divided by the mean count rate between normal right and left lung parenchyma.

A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.

Background: Improved usage of the repertoires of pancreatic ductal adenocarcinoma (PDAC) profiles is crucially needed to guide the development of predictive and prognostic tools that could inform the selection of treatment options.

Methods: Using publicly available mRNA abundance datasets, we performed a large retrospective meta-analysis on 466 PDAC patients to discover prognostic gene signatures. These signatures were trained on two clinical cohorts (n = 70), and validated on four independent clinical cohorts (n = 246).

Looking outside the "cardiac" box: incidental detection of a metastatic lung tumor on cardiac position emission tomography/computed tomography.

Incidental extracardiac findings are not uncommon in patients undergoing cardiac positron emission tomography/computed tomography (PET/CT) and some of these findings can have significant clinical impact. We report a case of a 74-year-old man who presented with dyspnea and left sided chest pain. 82-rubidium PET/CT imaging showed normal myocardial perfusion.

Perforin gene transfer into hematopoietic stem cells improves immune dysregulation in murine models of perforin deficiency.

Defects in perforin lead to the failure of T and NK cell cytotoxicity, hypercytokinemia, and the immune dysregulatory condition known as familial hemophagocytic lymphohistiocytosis (FHL). The only curative treatment is allogeneic hematopoietic stem cell transplantation which carries substantial risks. We used lentiviral vectors (LV) expressing the human perforin gene, under the transcriptional control of the ubiquitous phosphoglycerate kinase promoter or a lineage-specific perforin promoter, to correct the defect in different murine models.

Pulmonary macrophage transplantation therapy.

Bone-marrow transplantation is an effective cell therapy but requires myeloablation, which increases infection risk and mortality. Recent lineage-tracing studies documenting that resident macrophage populations self-maintain independently of haematological progenitors prompted us to consider organ-targeted, cell-specific therapy. Here, using granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor-β-deficient (Csf2rb(-/-)) mice that develop a myeloid cell disorder identical to hereditary pulmonary alveolar proteinosis (hPAP) in children with CSF2RA or CSF2RB mutations, we show that pulmonary macrophage transplantation (PMT) of either wild-type or Csf2rb-gene-corrected macrophages without myeloablation was safe and well-tolerated and that one administration corrected the lung disease, secondary systemic manifestations and normalized disease-related biomarkers, and prevented disease-specific mortality.

Metal artefact reduction algorithms prevent false positive results when assessing patients for cardiac implantable electronic device infection.

Software-based metal artefact reduction (MAR) techniques are available to reduce artefacts from cardiac implantable electronic devices (CIED) in the CT data. The impact of disabling MAR techniques on quantification of 18F-FDG uptake around the CIED has not been examined. We consider the importance of enabling MAR in patients with suspected CIED infection to prevent inaccuracies in quantification of tissue tracer uptake on the attenuation-corrected PET images.

Pancreatic cancer organotypics: High throughput, preclinical models for pharmacological agent evaluation.

Pancreatic cancer carries a terrible prognosis, as the fourth most common cause of cancer death in the Western world. There is clearly a need for new therapies to treat this disease. One of the reasons no effective treatment has been developed in the past decade may in part, be explained by the diverse influences exerted by the tumour microenvironment.

Identification of a cytotoxic form of dimeric interleukin-2 in murine tissues.

Interleukin-2 (IL-2) is a multi-faceted cytokine, known for promoting proliferation, survival, and cell death depending on the cell type and state. For example, IL-2 facilitates cell death only in activated T cells when antigen and IL-2 are abundant. The availability of IL-2 clearly impacts this process.

Comparison of occupational radiation exposure from myocardial perfusion imaging with Rb-82 PET and Tc-99m SPECT.

Objective: Rubidium-82 (Rb-82) PET myocardial perfusion imaging (MPI) has superior diagnostic accuracy, at least similar prognostic value, and lower patient radiation exposure when compared with technetium-99m single-photon emission computed tomography (Tc-99m SPECT) MPI. The aim of this study was to compare occupational radiation exposure from the two modalities and show that improvements for the patient do not come at a cost to staff.

Materials And Methods: Electronic personal dosimeters were worn by staff involved in the administration and imaging of routine clinical Tc-99m SPECT and Rb-82 PET MPI, and during tracer production and QC.

The Rim15-endosulfine-PP2ACdc55 signalling module regulates entry into gametogenesis and quiescence via distinct mechanisms in budding yeast.

Quiescence and gametogenesis represent two distinct survival strategies in response to nutrient starvation in budding yeast. Precisely how environmental signals are sensed by yeast cells to trigger quiescence and gametogenesis is not fully understood. A conserved signalling module consisting of Greatwall kinase, Endosulfine and Protein Phosphatase PP2ACdc55 proteins regulates entry into mitosis in Xenopus egg extracts and meiotic maturation in flies.

Designation of type genus for the holothuroid family Cucumellidae (Echinodermata : Holothuroidea : Dendrochirotida) with re-examination of the holotype of Cucumella decaryi Cherbonnier.

Thandar & Arumugam (2011), in their erection of the new dactylochirotid family Cucumellidae, inadvertently omitted to designate its type genus. This error is here rectified and Cucumella Heding (in Ludwig & Heding, 1935) is designated the type genus of the new family Cucumellidae to comply with the requirements of Article 61 of the International Code. Following Smirnov (2012), in his revised classification of the Holothuroidea, the new family is now classified in the order Dendrochirotida.

Highly ordered molecular films on Au(111): the N-heteroacene approach.

This study presents an innovative synthesis of dihydrotetraazapentacene (DHTAP) and the scanning tunneling microscopy (STM) investigation of the initial stages of its growth on Au(111). We were able to demonstrate that, up to the fourth monolayer, the DHTAP films show a high structural order and growths in perfect epitaxy. This behavior can be unequivocally attributed to the stabilizing effect of intralayer hydrogen bonding interactions.

A comparison between upright and supine myocardial perfusion imaging with attenuation correction.

Objective: The Digirad Cardius XACT is an upright myocardial perfusion imaging (MPI) single photon emission computed tomography system offering low-dose computed tomography for attenuation correction (AC). This study compares patient acceptability and image appearance for both non-AC and AC images on the XACT with supine MPI performed on a GE Infinia Hawkeye.

Patients And Methods: A total of 47 patients [29 male patients; mean (range) BMI, 29.

Impact of point spread function modeling and time-of-flight on myocardial blood flow and myocardial flow reserve measurements for rubidium-82 cardiac PET.

Background: Myocardial flow reserve (MFR) obtained from dynamic cardiac positron emission tomography (PET) with rubidium-82 (Rb-82) has been shown to be a useful measurement in assessing coronary artery disease. Advanced PET reconstructions with point spread function modeling and time-of-flight have been shown to improve image quality but also have an impact on kinetic analysis of dynamic data. This study aims to determine the impact of these algorithms on MFR data.