Immunoreactivity of the 14F7 Mab Raised against N-Glycolyl GM3 Ganglioside in Epithelial Malignant Tumors from Digestive System

The limited expression of N-Glycolyl GM3 (NeuGcGM3) ganglioside in human normal tissues, as well as its presence in melanoma and breast carcinoma using 14F7 Mab (anti-NeuGcGM3), has been previously reported. In this work we evaluated for the first time the 14F7 Mab immunorecognition in some digestive system tumors. Immunohistochemical assays were made with 14F7, followed by anti-mouse biotinylated antibody and ABC/HRP system in normal and pathological human tissues were made. No immunoreaction was evidenced in normal tissues. The reactivity of 14F7 was detected in all adenocarcinomas of the stomach (12/12), colon (12/12), and pancreas (11/11). A finely granular immunorecognition in esophageal tumors (5/15), epidermoid carcinoma of the rectum (5/7), and basaloid carcinoma (4/5) of the latter as well as in hepatocellular carcinoma (13/14) was also observed. Our results are in agreement with the assumption that NeuGcGM3 ganglioside may be considered as target for passive and active immunotherapy in digestive system malignancies expressing this molecule

Preoperative Imaging for Perforator Flaps in Reconstructive Surgery

Background: Although preoperative imaging of perforator vasculature in planning microvascular reconstruction is commonplace, there has not been any clear demonstration of the evidence for this practice, or data comparing the many available modalities in an evidence-based approach. This article aims to provide an objective, evidence-based review of the literature on this subject.\ud \ud Methods: The evidence supporting the use of various modalities of imaging was investigated by performing focused searches of the PubMed and Medline databases. The articles were ranked according to the criteria set out in March 2009 Oxford Centre for Evidence-Based Medicine definitions. Endpoints comprised objective outcome data supporting the use of imaging, including flap loss, unplanned returns to theater, operative time reduction, and surgeon-reported stress.\ud \ud Results: The objective high level of evidence for any form of preoperative perforator imaging is low with only small number of comparative studies or case series investigating computed tomographic angiography (CTA), magnetic resonance angiography, handheld Doppler, color duplex, and classic angiography. Of all modalities, there is a growing body of level 2b evidence supporting the use of CTA.\ud \ud Conclusion: While further multicenter trials testing hard outcomes are needed to conclusively validate preoperative imaging in reconstructive surgery, sufficient evidence exists to demonstrate that preoperative imaging can statistically improve outcomes, and that CTA is the current gold standard for perforator mapping

NGcGM3 Ganglioside: A Privileged Target for Cancer Vaccines

Active specific immunotherapy is a promising field in cancer research. N-glycolyl (NGc) gangliosides, and particularly NGcGM3, have received attention as a privileged target for cancer therapy. Many clinical trials have been performed with the anti-NGc-containing gangliosides anti-idiotype monoclonal antibody racotumomab (formerly known as 1E10) and the conjugated NGcGM3/VSSP vaccine for immunotherapy of melanoma, breast, and lung cancer. The present paper examines the role of NGc-gangliosides in tumor biology as well as the available preclinical and clinical data on these vaccine products. A brief discussion on the relevance of prioritization of cancer antigens in vaccine development is also included

CIGB-300, a proapoptotic peptide, inhibits angiogenesis in vitro and in vivo

We have previously demonstrated that a proapoptotic cyclic peptide CIGB-300, formerly known as P15-Tat delivered into the cells by the cell-penetrating peptide Tat, was able to abrogate the CK2-mediated phosphorylation and induce tumor regression when injected directly into solid tumors in mice or by systemic administration. In this work, we studied the role of CIGB-300 on the main events that take place in angiogenesis. At non-cytotoxic doses, CIGB-300 was able to inhibit adhesion, migration, and tubular network formation induced by human umbilical vein endothelial cells (HUVEC) growing upon Matrigel in vitro. Likewise, we evaluated the cellular penetration and localization into the HUVEC cells of CIGB-300. Our results confirmed a quick cellular penetration and a cytoplasmic accumulation in the early minutes of incubation and a translocation into the nuclei beginning at 12h of treatment, with a strong presence in the perinuclear area. A microarray analysis was used to determine the genes affected by the treatment. We observed that CIGB-300 significantly decreased four genes strongly associated with tubulogenesis, growth, and differentiation of endothelial cells. The CIGB-300 was tested in vivo on chicken embryo chorioallantoic membranes (CAM), and a large number of newly formed blood vessels were significantly regressed. The results suggested that CIGB-300 has a potential as an antiangiogenic treatment. The mechanism of action may be associated with partial inhibition of VEGF and Notch pathways.Fil: Farina, Hernán Gabriel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Benavent Acero, Fernando Rodrigo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Perera, Yasser. Center for Genetic Engineering and Biotechnology; CubaFil: Rodríguez, Arielis. Center for Genetic Engineering and Biotechnology; CubaFil: Perea, Silvio E.. Center for Genetic Engineering and Biotechnology; CubaFil: Acevedo Castro, Boris. Center for Genetic Engineering and Biotechnology; CubaFil: Gomez, Roberto. No especifíca;Fil: Alonso, Daniel F.. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Transits against Fainter Stars: The Power of Image Deconvolution

Compared to bright star searches, surveys for transiting planets against fainter (V=12-18) stars have the advantage of much higher sky densities of dwarf star primaries, which afford easier detection of small transiting bodies. Furthermore, deep searches are capable of probing a wider range of stellar environments. On the other hand, for a given spatial resolution and transit depth, deep searches are more prone to confusion from blended eclipsing binaries. We present a powerful mitigation strategy for the blending problem that includes the use of image deconvolution and high resolution imaging. The techniques are illustrated with Lupus-TR-3 and very recent IR imaging with PANIC on Magellan. The results are likely to have implications for the CoRoT and KEPLER missions designed to detect transiting planets of terrestrial size

The IsoDAR high intensity H2+ transport and injection tests

This technical report reviews the tests performed at the Best Cyclotron Systems, Inc. facility in regards to developing a cost effective ion source, beam line transport system, and acceleration system capable of high H[subscript 2][superscript +] current output for the IsoDAR (Isotope Decay At Rest) experiment. We begin by outlining the requirements for the IsoDAR experiment then provide overviews of the Versatile Ion Source (VIS), Low Energy Beam Transport (LEBT) system, spiral inflector, and cyclotron. The experimental measurements are then discussed and the results are compared with a thorough set of simulation studies. Of particular importance we note that the VIS proved to be a reliable ion source capable of generating a large amount of H[subscript 2][superscript +] current. The results suggest that with further upgrades, the VIS could potentially be a suitable candidate for IsoDAR. The conclusion outlines the key results from our tests and introduces the forthcoming work this technical report has motivated.National Science Foundation (U.S.) (PHY-1148134)Massachusetts Institute of Technology (Seed Fund)Massachusetts Institute of Technology (Bose Fellowship

Neoadjuvant in situ vaccination with cowpea mosaic virus as a novel therapy against canine inflammatory mammary cancer

BackgroundInflammatory mammary cancer (IMC), the counterpart of human inflammatory breast cancer (IBC), is the deadliest form of canine mammary tumors. IMC patients lack specific therapy and have poor outcomes. This proof-of-principle preclinical study evaluated the efficacy, safety, and effect on survival of neoadjuvant intratumoral (in situ) empty cowpea mosaic virus (eCPMV) immunotherapy in companion dogs diagnosed with IMC.MethodsTen IMC-bearing dogs were enrolled in the study. Five dogs received medical therapy, and five received weekly neoadjuvant in situ eCPMV immunotherapy (0.2–0.4 mg per injection) and medical therapy after the second eCPMV injection. Efficacy was evaluated by reduction of tumor growth; safety by hematological and biochemistry changes in blood and plasma; and patient outcome by survival analysis. eCPMV-induced immune changes in blood cells were analyzed by flow cytometry; changes in the tumor microenvironment were evaluated by CD3 (T lymphocytes), CD20 (B lymphocytes), FoxP3 (Treg lymphocytes), myeloperoxidase (MPO; neutrophils), Ki-67 (proliferation index, PI; tumor cell proliferation), and Cleaved Caspase-3 (CC-3; apoptosis) immunohistochemistry.ResultsTwo neoadjuvant in situ eCPMV injections resulted in tumor shrinkage in all patients by day 14 without systemic adverse events. Although surgery for IMC is generally not an option, reduction in tumor size allowed surgery in two IMC patients. In peripheral blood, in situ eCPMV immunotherapy was associated with a significant decrease of Treg$^{+}$/CD8$^{+}$ ratio and changes in CD8$^{+}$Granzyme B$^{+}$ T cells, which behave as a lagging predictive biomarker. In the TME, higher neutrophilic infiltration and MPO expression, lower tumor Ki-67 PI, increase in CD3$^{+}$ lymphocytes, decrease in FoxP3$^{+}$/CD3$^{+}$ ratio (p<0.04 for all comparisons), and no changes in CC-3$^{+}$ immunostainings were observed in post-treatment tumor tissues when compared with pretreatment tumor samples. eCPMV-treated IMC patients had a statistically significant (p=0.033) improved overall survival than patients treated with medical therapy.ConclusionsNeoadjuvant in situ eCPMV immunotherapy demonstrated anti-tumor efficacy and improved survival in IMC patients without systemic adverse effects. eCPMV-induced changes in immune cells point to neutrophils as a driver of immune response. Neoadjuvant in situ eCPMV immunotherapy could be a groundbreaking immunotherapy for canine IMC and a potential future immunotherapy for human IBC patients

Cold atoms in space : community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies

Predicción del éxito de la desfibrilación mediante entropía difusa en términos de recuperación de ritmo cardíaco regular, pulso y supervivencia

El objetivo de este trabajo es evaluar la capacidad predictiva de la entropía difusa (FuzzEn) para la predicción del éxito de la desfibrilación definida de tres formas diferentes: recuperación de ritmos con QRS, retorno de la circulación espontanea (RCE) y supervivencia del paciente. Se han analizado 450 descargas de 174 episodios de parada cardiorrespiratoria extrahospitalaria (PCREH). FuzzEn se calculó tomando 5-seg de fibrilación ventricular (FV) previos a la descarga. Se evaluó la capacidad de predicción en términos de área bajo la curva (AUC), para las primeras tres descargas. Para ello se ajustó un clasificador basado en regresión logística usando una partición 60/40 por pacientes para ajustar el modelo (desarrollo) y evaluar el AUC (validación). Los valores de AUC obtenidos para predicción de aparición de ritmos con QRS y supervivencia para las tres primeras descargas fueron: 0.81/0.70, 0.84/0.87 y 0.95/0.95, respectivamente. FuzzEn permite predecir la supervivencia del paciente y la predictibilidad mejora en descargas sucesivas