CRIS

Permanent URI for this communityhttps://investigadores.udd.cl/handle/123456789/1

Browse

Search Results

Now showing 1 - 7 of 7

Some of the metrics are blocked by your
consent settings
Validation of an NGS Panel Designed for Detection of Actionable Mutations in Tumors Common in Latin America
(2021)
Mauricio Salvo
;
Evelin González-Feliú
;
Jessica Toro
;
Iván Gallegos
;
Ignacio Maureira
<jats:p>Next-generation sequencing (NGS) is progressively being used in clinical practice. However, several barriers preclude using this technology for precision oncology in most Latin American countries. To overcome some of these barriers, we have designed a 25-gene panel that contains predictive biomarkers for most current and near-future available therapies in Chile and Latin America. Library preparation was optimized to account for low DNA integrity observed in formalin-fixed paraffin-embedded tissue. The workflow includes an automated bioinformatic pipeline that accounts for the underrepresentation of Latin Americans in genome databases. The panel detected small insertions, deletions, and single nucleotide variants down to allelic frequencies of 0.05 with high sensitivity, specificity, and reproducibility. The workflow was validated in 272 clinical samples from several solid tumor types, including gallbladder (GBC). More than 50 biomarkers were detected in these samples, mainly in BRCA1/2, KRAS, and PIK3CA genes. In GBC, biomarkers for PARP, EGFR, PIK3CA, mTOR, and Hedgehog signaling inhibitors were found. Thus, this small NGS panel is an accurate and sensitive method that may constitute a more cost-efficient alternative to multiple non-NGS assays and costly, large NGS panels. This kind of streamlined assay with automated bioinformatics analysis may facilitate the implementation of precision medicine in Latin America.</jats:p>
2Scopus© Citations 13
Some of the metrics are blocked by your
consent settings
New Markers for Cardiovascular Disease in Psoriatic Patients: Preliminary Study on Monocyte Phenotype, ADAMTS7, and mTOR Activity
(2023)
Khanty Loyola
;
Claudio Karsulovic
;
CABRERA MORAGA, RAUL ALEJANDRO
;
Claudio Perez
;
HOJMAN CANO, LIA PAULA
<jats:p>Psoriasis is a skin disease with occasional involvement of non-cutaneous territories. Beyond the usual, cardiovascular events are more frequent in these patients and correlate only partially with disease activity, suggesting the presence of other unknown factors. We selected ten psoriatic patients without treatment in the last year and matched them for age and gender with eleven healthy subjects. Ficoll-extracted mononuclear cells were analyzed with flow cytometry for monocyte surface phenotype markers, intracellular NFκB/inflammasome-dependent interleukins, and chemotaxis receptor CXCR3. Using ELISA, patient serum was evaluated for ADAMTS7 and CXCL10. Inflammatory M1 monocytes showed higher levels of IL-1β and IL-6 in psoriatic patients. M2 monocytes also showed higher levels of intracellular inflammatory cytokines. Nevertheless, IL-6 values were higher compared to other monocytes and IL-1β. The mTORC activation markers ADAMTS7 and S6Rp were higher in psoriatic patients than in healthy controls. In psoriatic patients, serum levels of ADAMTS7 were elevated, and M2 monocytes showed a distinct inflammatory response with higher relative levels of NFκB-dependent IL-6 and less activity of the CXCR3–CXCL10 chemotactic pathway. These data suggest pathways with potential markers for prediction and early detection of cardiovascular risk in psoriatic patients.</jats:p>
41Scopus© Citations 5
Some of the metrics are blocked by your
consent settings
MET Signaling Pathways, Resistance Mechanisms, and Opportunities for Target Therapies
(2022)
RIVAS VERA, SOLANGE VERÓNICA
;
Arnaldo Marín
;
Suraj Samtani
;
Evelin González-Feliú
;
ARMISEN YAÑEZ, RICARDO AMADO
<jats:p>The MET gene, known as MET proto-oncogene receptor tyrosine kinase, was first identified to induce tumor cell migration, invasion, and proliferation/survival through canonical RAS-CDC42-PAK-Rho kinase, RAS-MAPK, PI3K-AKT-mTOR, and β-catenin signaling pathways, and its driver mutations, such as MET gene amplification (METamp) and the exon 14 skipping alterations (METex14), activate cell transformation, cancer progression, and worse patient prognosis, principally in lung cancer through the overactivation of their own oncogenic and MET parallel signaling pathways. Because of this, MET driver alterations have become of interest in lung adenocarcinomas since the FDA approval of target therapies for METamp and METex14 in 2020. However, after using MET target therapies, tumor cells develop adaptative changes, favoring tumor resistance to drugs, the main current challenge to precision medicine. Here, we review a link between the resistance mechanism and MET signaling pathways, which is not only limited to MET. The resistance impacts MET parallel tyrosine kinase receptors and signals shared hubs. Therefore, this information could be relevant in the patient’s mutational profile evaluation before the first target therapy prescription and follow-up to reduce the risk of drug resistance. However, to develop a resistance mechanism to a MET inhibitor, patients must have access to the drugs. For instance, none of the FDA approved MET inhibitors are registered as such in Chile and other developing countries. Constant cross-feeding between basic and clinical research will thus be required to meet future challenges imposed by the acquired resistance to targeted therapies.</jats:p>
Scopus© Citations 15 16
Some of the metrics are blocked by your
consent settings
Key Role of Astrocytes in Postnatal Brain and Retinal Angiogenesis
(2022)
Mariela Puebla
;
Pablo J. Tapia
;
Hilda Espinoza
<jats:p>Angiogenesis is a key process in various physiological and pathological conditions in the nervous system and in the retina during postnatal life. Although an increasing number of studies have addressed the role of endothelial cells in this event, the astrocytes contribution in angiogenesis has received less attention. This review is focused on the role of astrocytes as a scaffold and in the stabilization of the new blood vessels, through different molecules release, which can modulate the angiogenesis process in the brain and in the retina. Further, differences in the astrocytes phenotype are addressed in glioblastoma, one of the most devastating types of brain cancer, in order to provide potential targets involved in the cross signaling between endothelial cells, astrocytes and glioma cells, that mediate tumor progression and pathological angiogenesis. Given the relevance of astrocytes in angiogenesis in physiological and pathological conditions, future studies are required to better understand the interrelation between endothelial and astrocyte signaling pathways during this process.</jats:p>
2Scopus© Citations 39
Some of the metrics are blocked by your
consent settings
Integrin Alpha E (CD103) Limits Virus-Induced IFN-I Production in Conventional Dendritic Cells
(2021)
Vikas Duhan
;
Vishal Khairnar
;
Simo Kitanovski
;
Thamer A. Hamdan
;
KLEIN POSTERNACK, ANDRES DAVID
<jats:p>Early and strong production of IFN-I by dendritic cells is important to control vesicular stomatitis virus (VSV), however mechanisms which explain this cell-type specific innate immune activation remain to be defined. Here, using a genome wide association study (GWAS), we identified Integrin alpha-E (<jats:italic>Itgae</jats:italic>, CD103) as a new regulator of antiviral IFN-I production in a mouse model of vesicular stomatitis virus (VSV) infection. CD103 was specifically expressed by splenic conventional dendritic cells (cDCs) and limited IFN-I production in these cells during VSV infection. Mechanistically, CD103 suppressed AKT phosphorylation and mTOR activation in DCs. Deficiency in CD103 accelerated early IFN-I in cDCs and prevented death in VSV infected animals. In conclusion, CD103 participates in regulation of cDC specific IFN-I induction and thereby influences immune activation after VSV infection.</jats:p>
1Scopus© Citations 4
Some of the metrics are blocked by your
consent settings
Editorial: Physiology of Myelin Forming Cells, From Myelination to Neural Modulators
(2019)
Marion Baraban
;
RETAMAL LUCERO, MAURICIO ANTONIO
;
Fernando C. Ortiz
11
Some of the metrics are blocked by your
consent settings
Cell Intrinsic and Extrinsic Mechanisms of Caveolin-1-Enhanced Metastasis
(2019)
America Campos
;
Renato Burgos-Ravanal
;
Maria Fernanda Gonzalez
;
Ricardo Huilcaman
;
LOBOS GONZALEZ, LORENA DE LOURDES
<jats:p>Caveolin-1 (CAV1) is a scaffolding protein with a controversial role in cancer. This review will initially discuss earlier studies focused on the role as a tumor suppressor before elaborating subsequently on those relating to function of the protein as a promoter of metastasis. Different mechanisms are summarized illustrating how CAV1 promotes such traits upon expression in cancer cells (intrinsic mechanisms). More recently, it has become apparent that CAV1 is also a secreted protein that can be included into exosomes where it plays a significant role in determining cargo composition. Thus, we will also discuss how CAV1 containing exosomes from metastatic cells promote malignant traits in more benign recipient cells (extrinsic mechanisms). This ability appears, at least in part, attributable to the transfer of specific cargos present due to CAV1 rather than the transfer of CAV1 itself. The evolution of how our perception of CAV1 function has changed since its discovery is summarized graphically in a time line figure.</jats:p>
1 2Scopus© Citations 52

CRIS

Browse

Filters

Settings

Sort By

Results per page

Search Results