Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
Add more filters











Publication year range
2.
Sci Rep ; 11(1): 14426, 2021 07 13.
Article in English | MEDLINE | ID: mdl-34257359

ABSTRACT

Identification of the different elements intervening at the tumor microenvironment seems key to explain clinical evolution in several tumor types. In this study, a set of immune biomarkers (myeloid derived suppressor cells, regulatory T cells, and OX40 + and PD-1 + T lymphocytes counts) in peripheral blood of patients diagnosed with advanced breast cancer were analyzed along of first line antineoplastic therapy. Subsequently, a comparison between groups with clinical benefit versus progression of disease and with a healthy women cohort was executed. Results reflected that patients showed higher basal levels of myeloid derived suppressor cells (35.43, IR = 180.73 vs 17.53, IR = 16.96 cells/µl; p = 0.001) and regulatory T cells (32.05, IR = 29.84 vs 22.61, IR = 13.57 cells/µl; p = 0.001) in comparison with healthy women. Furthermore, an increase in the number of activated T lymphocytes (expressing OX40), a decrease of immune inhibitory cells (MDSCs and Tregs) and inhibited T lymphocytes (expressing PD-1) were observed along the treatment in patients with clinical benefit (p ≤ 0.001). The opposite trend was observed in the case of disease progression. These findings suggest that some critical immune elements can be easily detected and measured in peripheral blood, which open a new opportunity for translational research, as they seem to be correlated with clinical evolution, at least in ABC.


Subject(s)
Breast Neoplasms , Myeloid-Derived Suppressor Cells , Female , Humans , Lymphocyte Count , T-Lymphocytes, Regulatory , Tumor Microenvironment
3.
mBio ; 6(4)2015 Aug 25.
Article in English | MEDLINE | ID: mdl-26307166

ABSTRACT

UNLABELLED: Describing the viral diversity of wildlife can provide interesting and useful insights into the natural history of established human pathogens. In this study, we describe a previously unknown picornavirus in harbor seals (tentatively named phopivirus) that is related to human hepatitis A virus (HAV). We show that phopivirus shares several genetic and phenotypic characteristics with HAV, including phylogenetic relatedness across the genome, a specific and seemingly quiescent tropism for hepatocytes, structural conservation in a key functional region of the type III internal ribosomal entry site (IRES), and a codon usage bias consistent with that of HAV. IMPORTANCE: Hepatitis A virus (HAV) is an important viral hepatitis in humans because of the substantial number of cases each year in regions with low socioeconomic status. The origin of HAV is unknown, and no nonprimate HAV-like viruses have been described. Here, we describe the discovery of an HAV-like virus in seals. This finding suggests that the diversity and evolutionary history of these viruses might be far greater than previously thought and may provide insight into the origin and pathogenicity of HAV.


Subject(s)
Hepatovirus/genetics , Hepatovirus/isolation & purification , Phylogeny , Seals, Earless/virology , Animals , Codon , Genome, Viral , Genotype , Hepatitis A Virus, Human/genetics , Hepatovirus/physiology , High-Throughput Nucleotide Sequencing , Humans , Liver/virology , Lung/virology , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , Spleen/virology , Virus Replication
4.
Ecohealth ; 11(2): 255-7, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24504904

ABSTRACT

West Nile virus (WNV) first emerged in the US in 1999 and has since spread across the Americas. Here, we report the continued expansion of WNV to the British Virgin Islands following its emergence in a flock of free-roaming flamingos. Histologic review of a single chick revealed lesions consistent with WNV infection, subsequently confirmed with PCR, immunohistochemistry and in situ hybridization. Full genome analysis revealed 99% sequence homology to strains circulating in the US over the past decade. This study highlights the need for rapid necropsy of wild bird carcasses to fully understand the impact of WNV on wild populations.


Subject(s)
Bird Diseases/epidemiology , Bird Diseases/virology , Culex/virology , Disease Outbreaks/veterinary , Insect Vectors/virology , West Nile Fever/epidemiology , West Nile virus/isolation & purification , Animals , Animals, Wild/virology , Bird Diseases/transmission , Birds/virology , Bites and Stings/virology , British Virgin Islands , Immunohistochemistry , In Situ Hybridization , Polymerase Chain Reaction , West Nile Fever/transmission , West Nile Fever/virology , West Nile virus/genetics
5.
J Gen Virol ; 94(Pt 5): 1028-1038, 2013 May.
Article in English | MEDLINE | ID: mdl-23364191

ABSTRACT

Bats are reservoirs for a wide range of human pathogens including Nipah, Hendra, rabies, Ebola, Marburg and severe acute respiratory syndrome coronavirus (CoV). The recent implication of a novel beta (ß)-CoV as the cause of fatal respiratory disease in the Middle East emphasizes the importance of surveillance for CoVs that have potential to move from bats into the human population. In a screen of 606 bats from 42 different species in Campeche, Chiapas and Mexico City we identified 13 distinct CoVs. Nine were alpha (α)-CoVs; four were ß-CoVs. Twelve were novel. Analyses of these viruses in the context of their hosts and ecological habitat indicated that host species is a strong selective driver in CoV evolution, even in allopatric populations separated by significant geographical distance; and that a single species/genus of bat can contain multiple CoVs. A ß-CoV with 96.5 % amino acid identity to the ß-CoV associated with human disease in the Middle East was found in a Nyctinomops laticaudatus bat, suggesting that efforts to identify the viral reservoir should include surveillance of the bat families Molossidae/Vespertilionidae, or the closely related Nycteridae/Emballonuridae. While it is important to investigate unknown viral diversity in bats, it is also important to remember that the majority of viruses they carry will not pose any clinical risk, and bats should not be stigmatized ubiquitously as significant threats to public health.


Subject(s)
Chiroptera/virology , Coronavirus Infections/veterinary , Coronavirus/isolation & purification , Genetic Variation , Animals , Base Sequence , Coronavirus/classification , Coronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , DNA, Complementary/chemistry , DNA, Complementary/genetics , Disease Reservoirs , Ecosystem , Humans , Mexico/epidemiology , Molecular Sequence Data , Phylogeny , Public Health , RNA, Viral/genetics , Sequence Analysis, DNA , Zoonoses
6.
mBio ; 3(4): e00166-12, 2012.
Article in English | MEDLINE | ID: mdl-22851656

ABSTRACT

UNLABELLED: From September to December 2011, 162 New England harbor seals died in an outbreak of pneumonia. Sequence analysis of postmortem samples revealed the presence of an avian H3N8 influenza A virus, similar to a virus circulating in North American waterfowl since at least 2002 but with mutations that indicate recent adaption to mammalian hosts. These include a D701N mutation in the viral PB2 protein, previously reported in highly pathogenic H5N1 avian influenza viruses infecting people. Lectin staining and agglutination assays indicated the presence of the avian-preferred SAα-2,3 and mammalian SAα-2,6 receptors in seal respiratory tract, and the ability of the virus to agglutinate erythrocytes bearing either the SAα-2,3 or the SAα-2,6 receptor. The emergence of this A/harbor seal/Massachusetts/1/2011 virus may herald the appearance of an H3N8 influenza clade with potential for persistence and cross-species transmission. IMPORTANCE: The emergence of new strains of influenza virus is always of great public concern, especially when the infection of a new mammalian host has the potential to result in a widespread outbreak of disease. Here we report the emergence of an avian influenza virus (H3N8) in New England harbor seals which caused an outbreak of pneumonia and contributed to a U.S. federally recognized unusual mortality event (UME). This outbreak is particularly significant, not only because of the disease it caused in seals but also because the virus has naturally acquired mutations that are known to increase transmissibility and virulence in mammals. Monitoring the spillover and adaptation of avian viruses in mammalian species is critically important if we are to understand the factors that lead to both epizootic and zoonotic emergence.


Subject(s)
Communicable Diseases, Emerging/veterinary , Influenza A Virus, H3N8 Subtype/isolation & purification , Orthomyxoviridae Infections/veterinary , Phoca/virology , Pneumonia/veterinary , Animals , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/virology , Disease Outbreaks , Humans , Influenza A Virus, H3N8 Subtype/classification , Influenza A Virus, H3N8 Subtype/genetics , Influenza A Virus, H3N8 Subtype/pathogenicity , Influenza A Virus, H5N1 Subtype/genetics , Influenza A Virus, H5N1 Subtype/isolation & purification , Influenza, Human/virology , Molecular Sequence Data , Mutation , New England/epidemiology , Orthomyxoviridae Infections/epidemiology , Orthomyxoviridae Infections/virology , Phylogeny , Pneumonia/epidemiology , Pneumonia/virology , Viral Proteins/genetics , Virulence
7.
Anticancer Res ; 31(9): 3019-25, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21868553

ABSTRACT

AIM: To characterize the differentially-activated mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K/Akt/mTOR) pathways in mutant (m) and wild-type (wt) GISTs and to investigate the role of insulin-like growth factor 1 receptor (IGF1R) expression. MATERIALS AND METHODS: Ninety-nine paraffin-embedded gastrointestinal stromal tumors (GISTs) were selected. CD117, IGF1R, phospho-ERK1/2, phospho-Akt, p70S6, eukaryotic initiation factor 4E-binding protein-1 (4EBP1) and pS6 expression were investigated using immunohistochemical methods. KIT exons 9, 11, 13 and 17 and platelet derived growth factor receptor alpha (PDGFRA) exons 12 and 18 were amplified by PCR and sequenced. RESULTS: Significant differences were found in the expression of phospho-ERK1/2 between mGISTs and wtGISTs. Complex evaluation of all PI3K/Akt/mTOR pathway markers revealed greater activation in mGISTs, particularly in PDGFRA-mutated GISTs. No significant correlation was observed between IGF1R expression and either mutational status or pathway activation. CONCLUSION: There appears to be no MAPK pathway activation in wtGISTs. Tumors harboring PDGFRA mutations tended to use the PI3K/Akt/mTOR signaling pathway. Most adult GISTs, irrespective of mutational status, displayed no IGFR1 expression; tumors positive for IGFR1 showed no preferential activation of the MAPK or AKT pathways.


Subject(s)
Gastrointestinal Stromal Tumors/metabolism , Mitogen-Activated Protein Kinases/metabolism , Protein Kinases/metabolism , Receptor, IGF Type 1/metabolism , Base Sequence , DNA Primers , Enzyme Activation , Gastrointestinal Stromal Tumors/enzymology , Humans
8.
Rev. esp. enferm. dig ; 102(8): 489-497, ago. 2010. tab, ilus
Article in Spanish | IBECS | ID: ibc-80928

ABSTRACT

Introducción: los tumores del estroma gastrointestinal (GIST)son neoplasias mesenquimales del tubo digestivo que generalmenteexpresan el receptor KIT (CD117) y muestran mutaciones enlos genes KIT o PDGFRA. Aunque la forma de presentación clínicahabitual es como una neoplasia mural solitaria, excepcionalmentepueden presentarse formas múltiples en el mismo o diferenteórgano.Objetivo: revisar las características morfológicas, inmunohistoquímicasy moleculares de las formas de GIST múltiples no metastásicos.Fuentes: revisión de la literatura en Medline y la propia experiencia.Conclusiones: los GIST múltiples pueden presentarse en trescontextos diferentes: lesiones espontáneas (del adulto o de la edadinfantil); síndrome familiar propio (transmitido con herencia autosómicadominante); y lesiones asociadas a síndromes específicos(tríada de Carney, síndrome de Carney-Stratakis, y neurofibromatosistipo I). Fuera de estos ámbitos, se interpreta que todo GISTmúltiple es el resultado de siembras tumorales metastásicas y, portanto, corresponde a enfermedad avanzada. Estas variantes debenser conocidas por el clínico dado las connotaciones pronósticas yterapéuticas que ello conlleva(AU)


Introduction: gastrointestinal stromal tumors (GISTs) are specific,generally KIT (CD117)-positive, mesenchymal tumors of thedigestive tract displaying KIT or PDGFRA gene mutations. Clinically,they tend to present as solitary tumors of the intestinal wall;more rarely, multiple tumors may occur in one or more organs.Objective: to review the morphological, immunohistochemicaland molecular features of multiple, non-metastatic forms ofGIST.Sources: review of the literature on Medline, and authors’own experience.Conclusions: multiples GISTs may occur in three differentcontexts: as spontaneous lesions (in both adults and children); dueto familial GIST syndrome (autosomal dominant inheritance); orin association with specific syndromes (e.g. Carney’s triad, Carney-Stratakis syndrome, type I neurofibromatosis). Outside thesecontexts, the existence of multiple GISTs is deemed to be the resultof tumor metastasis, and therefore indicative of advanced-stagedisease. Clinicians need to be aware of these variants, whoseprognosis and treatment differ(AU)


Subject(s)
Humans , Male , Female , Gastrointestinal Stromal Tumors/complications , Gastrointestinal Stromal Tumors/diagnosis , Neurofibromatosis 1/complications , Neurofibromatosis 1/diagnosis , Immunohistochemistry/methods , Immunohistochemistry , Gastrointestinal Stromal Tumors/physiopathology , Gastrointestinal Stromal Tumors , Neurofibromatosis 1/physiopathology , Neurofibromatosis 1
9.
Rev Esp Enferm Dig ; 102(8): 489-97, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20670070

ABSTRACT

INTRODUCTION: gastrointestinal stromal tumors (GISTs) are specific, generally KIT (CD117)-positive, mesenchymal tumors of the digestive tract displaying KIT or PDGFRA gene mutations. Clinically, they tend to present as solitary tumors of the intestinal wall; more rarely, multiple tumors may occur in one or more organs. OBJECTIVE: to review the morphological, immunohistochemical and molecular features of multiple, non-metastatic forms of GIST. SOURCES: review of the literature on Medline, and authors own experience. CONCLUSIONS: multiples GISTs may occur in three different contexts: as spontaneous lesions (in both adults and children); due to familial GIST syndrome (autosomal dominant inheritance); or in association with specific syndromes (e.g. Carney s triad, Carney-Stratakis syndrome, type I neurofibromatosis). Outside these contexts, the existence of multiple GISTs is deemed to be the result of tumor metastasis, and therefore indicative of advanced-stage disease. Clinicians need to be aware of these variants, whose prognosis and treatment differ.


Subject(s)
Gastrointestinal Stromal Tumors , Adult , Child , Gastrointestinal Stromal Tumors/genetics , Gastrointestinal Stromal Tumors/pathology , Humans
SELECTION OF CITATIONS
SEARCH DETAIL