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

Racotumomab: an anti=idiotype vaccine related to N=glycolyl=containing=gangliosides: Preclinical and clinical data

Neu-glycolyl (NeuGc)-containing gangliosides are attractive targets for immunotherapy with anti-idiotype mAbs, because these glycolipids are not normal components of the cytoplasmic membrane in humans, but their expression has been demonstrated in several human malignant tumors. Racotumomab is an anti-idiotype mAb specific to P3 mAb, an antibody which reacts to NeuGc-containing gangliosides, sulfatides, and other antigens expressed in tumors. Preparations containing racotumomab were able to induce a strong anti-metastatic effect in tumor-bearing mice. Different Phase I clinical trials have been conducted in patients with advanced melanoma, breast cancer, and lung cancer. The results of these clinical trials demonstrated the low toxicity and the high immunogenicity of this vaccine. The induced antibodies recognized and directly killed tumor cells expressing NeuGcGM3. A Phase II/III multicenter, controlled, randomized, double blind clinical trial was conducted to evaluate the effect of aluminum hydroxide-precipitated racotumomab vaccine in overall survival in patients with advanced non-small cell lung cancer. The clinical results of this study showed a significant clinical benefit in the patients who were treated with the anti-idiotype vaccine.Fil: Vazquez, Ana M.. Center of Molecular Immunology; CubaFil: Hernandez, Ana M.. Center of Molecular Immunology; CubaFil: Macias, Amparo. Center of Molecular Immunology; CubaFil: Montero, Enrique. Center of Molecular Immunology; CubaFil: Gomez, Daniel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Gomez, Roberto E.. Elea Laboratories; Argentin

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 12. h 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. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Benavent Acero, Fernando Rodrigo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; 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 Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

The Renormalization Group, Systems of Units and the Hierarchy Problem

In the context of the Renormalization Group (RG) for gravity I discuss the role of field rescalings and their relation to choices of units. I concentrate on a simple Higgs model coupled to gravity, where natural choices of units can be based on Newton's constant or on the Higgs mass. These quantities are not invariant under the RG, and the ratio between the units is scale-dependent. In the toy model, strong RG running occurs in the intermediate regime between the Higgs and the Planck scale, reproducing the results of the Randall-Sundrum I model. Possible connections with the problem of the mass hierarchy are pointed out.Comment: Plain TEX, 16 pages. Some revisions, some references adde

Characterization of Escherichia coli Carrying mcr-1-Plasmids Recovered From Food Animals From Argentina

In this study, we found mcr-1.1 and mcr-1.5 genes carried by IncI2 plasmids in a subset of Escherichia coli isolates recovered from commercial broiler farms in Argentina. The comparative analysis of the sequences of these plasmids with those described in human clinical isolates suggests that this replicon-type is one of the main mcr-disseminator sources in Argentina

Intra‐Amniotic Administration of HMGB1 Induces Spontaneous Preterm Labor and Birth

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116331/1/aji12443_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/116331/2/aji12443.pd

Replica Cluster Variational Method: the Replica Symmetric solution for the 2D random bond Ising model

We present and solve the Replica Symmetric equations in the context of the Replica Cluster Variational Method for the 2D random bond Ising model (including the 2D Edwards-Anderson spin glass model). First we solve a linearized version of these equations to obtain the phase diagrams of the model on the square and triangular lattices. In both cases the spin-glass transition temperatures and the tricritical point estimations improve largely over the Bethe predictions. Moreover, we show that this phase diagram is consistent with the behavior of inference algorithms on single instances of the problem. Finally, we present a method to consistently find approximate solutions to the equations in the glassy phase. The method is applied to the triangular lattice down to T=0, also in the presence of an external field.Comment: 22 pages, 11 figure

Mode coupling in the nonlinear response of black holes

We study the properties of the outgoing gravitational wave produced when a non-spinning black hole is excited by an ingoing gravitational wave. Simulations using a numerical code for solving Einstein's equations allow the study to be extended from the linearized approximation, where the system is treated as a perturbed Schwarzschild black hole, to the fully nonlinear regime. Several nonlinear features are found which bear importance to the data analysis of gravitational waves. When compared to the results obtained in the linearized approximation, we observe large phase shifts, a stronger than linear generation of gravitational wave output and considerable generation of radiation in polarization states which are not found in the linearized approximation. In terms of a spherical harmonic decomposition, the nonlinear properties of the harmonic amplitudes have simple scaling properties which offer an economical way to catalog the details of the waves produced in such black hole processes.Comment: 17 pages, 20 figures, abstract and introduction re-writte

New VVV Survey Globular Cluster Candidates in the Milky Way Bulge

© 2017 The American Astronomical Society. All rights reserved.It is likely that a number of Galactic globular clusters remain to be discovered, especially toward the Galactic bulge. High stellar density combined with high and differential interstellar reddening are the two major problems for finding globular clusters located toward the bulge. We use the deep near-IR photometry of the VISTA Variables in the Vía Láctea (VVV) Survey to search for globular clusters projected toward the Galactic bulge, and hereby report the discovery of 22 new candidate globular clusters. These objects, detected as high density regions in our maps of bulge red giants, are confirmed as globular cluster candidates by their color-magnitude diagrams. We provide their coordinates as well as their near-IR color-magnitude diagrams, from which some basic parameters are derived, such as reddenings and heliocentric distances. The color-magnitude diagrams reveal well defined red giant branches in all cases, often including a prominent red clump. The new globular cluster candidates exhibit a variety of extinctions (0.06 < A Ks < 2.77) and distances (5.3 < D < 9.5 kpc). We also classify the globular cluster candidates into 10 metal-poor and 12 metal-rich clusters, based on the comparison of their color-magnitude diagrams with those of known globular clusters also observed by the VVV Survey. Finally, we argue that the census for Galactic globular clusters still remains incomplete, and that many more candidate globular clusters (particularly the low luminosity ones) await to be found and studied in detail in the central regions of the Milky Way.Peer reviewedFinal Accepted Versio

Mutations in fetal genes involved in innate immunity and host defense against microbes increase risk of preterm premature rupture of membranes (PPROM)

BackgroundTwin studies have revealed a significant contribution of the fetal genome to risk of preterm birth. Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of preterm delivery. Infection and inflammation of the fetal membranes is commonly found associated with PPROM.MethodsWe carried out whole exome sequencing (WES) of genomic DNA from neonates born of Africanâ American mothers whose pregnancies were complicated by PPROM (76) or were normal term pregnancies (N = 43) to identify mutations in 35 candidate genes involved in innate immunity and host defenses against microbes. Targeted genotyping of mutations in the candidates discovered by WES was conducted on an additional 188 PPROM cases and 175 controls.ResultsWe identified rare heterozygous nonsense and frameshift mutations in several of the candidate genes, including CARD6, CARD8, DEFB1, FUT2, MBL2, NLP10, NLRP12, and NOD2. We discovered that some mutations (CARD6, DEFB1, FUT2, MBL2, NLRP10, NOD2) were present only in PPROM cases.ConclusionsWe conclude that rare damaging mutations in innate immunity and host defense genes, the majority being heterozygous, are more frequent in neonates born of pregnancies complicated by PPROM. These findings suggest that the risk of preterm birth in Africanâ Americans may be conferred by mutations in multiple genes encoding proteins involved in dampening the innate immune response or protecting the host against microbial infection and microbial products.Rare damaging mutations in fetal innate immunity and host defense genes, the majority being heterozygous, are more frequent in neonates born of pregnancies complicated by preterm premature rupture of membranes. An increased risk of preterm birth may be conferred by mutations in multiple genes encoding proteins involved in dampening the innate immune response or protecting the host against microbial infection and microbial products.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140041/1/mgg3330.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140041/2/mgg3330_am.pd