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Almada M.,University of Sonora | Leal-Martinez B.H.,University of Sonora | Hassan N.,Metropolitan University of Technology | Kogan M.J.,University of Chile | And 5 more authors.
Materials Science and Engineering C | Year: 2017

Gold nanorods (GNR) use has been proposed in medical applications because of their intrinsic photothermal properties. However, the presence of CTAB molecules adsorbed onto the surface of GNRs results in a highly cytotoxic GNR system. In this work we replace the CTAB molecules with a thiolated chitosan. Once chitosan coated GNRs (Chi-SH-GNR) were attained, a film of alginate (Alg-Chi-SH-GNR) or polyvinyl alcohol (PVA-Chi-SH-GNR) was deposited onto the surface of Chi-GNR by a layer-by-layer process. The photothermal conversion efficiency for the GNR systems was determined irradiating the GNRs suspended in aqua media with a CW 808 nm diode laser (CNI, China). The cytotoxicity effect and the photothermal cellular damage of GNR systems were evaluated on a breast cancer cell line. Results show that polymer coats did not affect the transduction photothermal efficiency. Values around 50% were obtained for the different coated gold nanorods. The cytotoxicity of coated gold nanorods diminished significantly compared with those GNR stabilized with CTAB. The laser irradiation of cells treated with gold nanorods showed a decrease in their viability compared with the cells treated but no irradiated. © 2017 Elsevier B.V.


Fernandez J.G.,University of Chile | Rodriguez D.A.,University of Chile | Rodriguez D.A.,St Jude Childrens Research Hospital | Valenzuela M.,University of Chile | And 13 more authors.
Molecular Cancer | Year: 2014

Early in cancer development, tumour cells express vascular endothelial growth factor (VEGF), a secreted molecule that is important in all stages of angiogenesis, an essential process that provides nutrients and oxygen to the nascent tumor and thereby enhances tumor-cell survival and facilitates growth. Survivin, another protein involved in angiogenesis, is strongly expressed in most human cancers, where it promotes tumor survival by reducing apoptosis as well as favoring endothelial cell proliferation and migration. The mechanisms by which cancer cells induce VEGF expression and angiogenesis upon survivin up-regulation remain to be fully established. Since the PI3K/Akt signalling and β-catenin-Tcf/Lef dependent transcription have been implicated in the expression of many cancer-related genes, including survivin and VEGF, we evaluated whether survivin may favor VEGF expression, release from tumor cells and induction of angiogenesis in a PI3K/Akt-β-catenin-Tcf/Lef-dependent manner. Here, we provide evidence linking survivin expression in tumor cells to increased β-catenin protein levels, β-catenin-Tcf/Lef transcriptional activity and expression of several target genes of this pathway, including survivin and VEGF, which accumulates in the culture medium. Alternatively, survivin downregulation reduced β-catenin protein levels and β-catenin-Tcf/Lef transcriptional activity. Also, using inhibitors of PI3K and the expression of dominant negative Akt, we show that survivin acts upstream in an amplification loop to promote VEGF expression. Moreover, survivin knock-down in B16F10 murine melanoma cells diminished the number of blood vessels and reduced VEGF expression in tumors formed in C57BL/6 mice. Finally, in the chick chorioallantoid membrane assay, survivin expression in tumor cells enhanced VEGF liberation and blood vessel formation. Importantly, the presence of neutralizing anti-VEGF antibodies precluded survivin-enhanced angiogenesis in this assay. These findings provide evidence for the existance of a posititve feedback loop connecting survivin expression in tumor cells to PI3K/Akt enhanced β-catenin-Tcf/Lef-dependent transcription followed by secretion of VEGF and angiogenesis. © 2014 Fernández et al.; licensee BioMed Central Ltd.


Morales J.O.,University of Chile | Morales J.O.,Advanced Center for Chronic Diseases iS | Valdes K.,University of Chile | Morales J.,University of Chile | And 2 more authors.
Nanomedicine | Year: 2015

Retinoids are lipophilic compounds that are highly used in cosmetics/therapeutics for skin disorders. Conventional formulations are limited by poor water solubility, high chemical/photochemical instability and the irritation of retinoids. Interestingly, lipid nanoparticles enable the administration of retinoids in aqueous media, providing drug stabilization and controlled release. Recently, it has been demonstrated that retinoids in solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and nanocapsules can decrease degradation, improve targeting and enhance efficacy for the treatment of skin disorders. This article focuses on the formulation, fabrication, characterization and in vitro/in vivo evaluation of solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and nanocapsules loaded with retinoids for skin administration. Furthermore, the incorporation of these lipid nanoparticles into secondary vehicles is discussed. © 2015 Future Medicine Ltd.


Foerster C.,Advanced Center for Chronic Diseases is | Figueroa G.,University of Chile | Evers E.,National Institute for Public Health and the Environment
British Food Journal | Year: 2015

Purpose – A quantitative microbiological risk assessment (QMRA) was developed to estimate the probability of getting listeriosis as a consequence of chicken and beef consumption in Chile. The paper aims to discuss these issues. Design/methodology/approach – As a first step a deterministic retail-to-home model was constructed for the Chilean susceptible population, including storage, cross-contamination and cooking. Next, two probabilisticmodels were developed, including variability and/or the uncertainty of some of the parameters. The probabilistic models were analyzed by Monte Carlo simulations with 100,000 iterations. Findings – Of the total susceptible population used in the model (2.81 million people), the deterministic model estimated 11 and two listeriosis cases because of beef and poultry consumption, respectively and the variability model estimated a mean of 322 and 7,546 cases for beef and poultry consumption, respectively. The uncertainty analysis showed large ranges, with realistic estimates made with an initial concentration of Listeria monocytogenes of 0.04-1 CFU/g and a dose-response parameter r ranging from 10-14 to 10-10. Research limitations/implications – The lack of information was the major limitation of the model, so the generation of it has to be a priority in Chile for developing less uncertain risk assessments in the future. Practical implications – Raw animal products can be the cause of listeriosis cases if they are not stored, cooked and/or handled properly. Consumer education seems to be an essential factor for disease prevention. Originality/value – This is the first QMRA made in Chile, and also the first study of listeriosis in non-processed meat. © Emerald Group Publishing Limited.


Vera C.,University of Chile | Tapia V.,University of Chile | Vega M.,University of Chile | Romero C.,University of Chile | Romero C.,Advanced Center for Chronic Diseases iS
Journal of Ovarian Research | Year: 2014

In normal ovarian function a controlled angiogenesis is essential. Several growth factors are involved in this process, such as the vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). The angiogenesis process in the normal ovary is a tightly controlled process that occurs in each ovarian cycle. Also, angiogenesis is critical for ovarian cancer development and it is responsible for tumor spread, metastasis and its peritoneal dissemination. Ovarian cancer is the fifth leading cause of cancer death in women and it is distinguished as the most lethal gynecologic cancer. In recent years angiogenesis has been given considerable attention in order to identify targets for developing effective anti-tumor therapies. Several molecules have been reported to promote angiogenesis, such as platelet-derived growth factor (PDGF) and its receptors, the angiopoietin/Tie ligand/receptor system and fibroblast growth factor (FGF). Primarily, VEGF has been identified to play key roles in driving angiogenesis. The above-mentioned molecules are candidate drug targets. Used in combination with other treatments, anti-angiogenic therapies have managed to reduce disease progression. The present review is focused in NGF and its high affinity receptor tyrosine kinase A (TRKA). The expression of VEGF, proliferation and the angiogenesis process in ovarian cancer is importantly induced by NGF, among other molecules. © 2014 Vera et al.; licensee BioMed Central Ltd.


Adura C.,University of Chile | Adura C.,University of Santiago de Chile | Guzman F.,Pontifical Catholic University of Valparaíso | Alvarez-Lueje A.,University of Chile | And 2 more authors.
Journal of the Chilean Chemical Society | Year: 2015

In this work, we report a fast and accessible method for quantification of cetyltrimethylammonium bromide (CTAB) in solutions of gold nanorods (GNRs) by bromophenol blue (BPB) ion-paring formation and spectrophotometric detection. The ion-par method used to quantify CTAB exhibited adequate figures of merit and was applied to the quantification of CTAB present in solutions of GNRs-CTAB and in GNRs-CLPFFD samples obtained by the seed growth method. This type of methodology could be extensive to others surfactants employed for the synthesis of nanoparticles. In addition, this method allows screening CTAB in GNRs samples and consequently would help to know if CTAB concentration is lower than an acceptable cut-off for cell viability analysis.


Guerrero A.R.,University of Chile | Guerrero A.R.,Advanced Center for Chronic Diseases iS | Hassan N.,University of Chile | Escobar C.A.,Andrés Bello University | And 6 more authors.
Nanomedicine | Year: 2014

In this article, we describe how nanoparticles work in photothermally triggered drug delivery, starting with a description of the plasmon resonance and the photothermal effect, and how this is used to release a drug. Then, we describe the four major functionalization strategies and each of their different applications. Finally, we discuss the biodistribution and toxicity of these systems and the necessary requirements for the use of gold nanoparticles for spatially and temporally controlling drug release through the photothermal effect. © 2014 Future Medicine Ltd.


Catalan-Figueroa J.,University of Chile | Palma-Florez S.,Advanced Center for Chronic Diseases iS | Alvarez G.,University of Chile | Fritz H.F.,University of Chile | And 3 more authors.
Nanomedicine | Year: 2016

Current strategies for brain diseases are mostly symptomatic and noncurative. Nanotechnology has the potential to facilitate the transport of drugs across the blood-brain barrier and to enhance their pharmacokinetic profile. However, to reach clinical application, an understanding of nanoneurotoxicity in terms of oxidative stress and inflammation is required. Emerging evidence has also shown that nanoparticles have the ability to alter autophagy, which can induce inflammation and oxidative stress, or vice versa. These effects may increase neurodegenerative processes damage, but on the other hand, they may have benefits for brain cancer therapies. In this review, we emphasize how nanomaterials may induce neurotoxic effects focusing on neurodegeneration, and how these effects could be exploited toward brain cancer treatment. © 2016 Future Medicine Ltd.


PubMed | University of Chile, University of Santiago de Chile and Advanced Center for Chronic Diseases iS
Type: | Journal: BMC cancer | Year: 2015

Caveolin-1 (CAV1) has been implicated both in tumor suppression and progression, whereby the specific role appears to be context dependent. Endometrial cancer is one of the most common malignancies of the female genital tract; however, little is known about the role of CAV1 in this disease.Here, we first determined by immunohistochemistry CAV1 protein levels in normal proliferative human endometrium and endometrial tumor samples. Then using two endometrial cancer cell lines (ECC: Ishikawa and Hec-1A) we evaluated mRNA and protein levels of CAV1 by real time qPCR and Western blot analysis, respectively. The role of CAV1 expression in ECC malignancy was further studied by either inducing its expression in endometrial cancer cells with the tumor promotor 12-O-tetradecanoyl-phorbol-13-acetate (4-TPA) or decreasing expression using short-hairpin RNA constructs, and then evaluating the effects of these changes on ECC proliferation, transmigration, matrigel invasion, and colony formation in soft agar.Immunohistochemical analysis of endometrial epithelia revealed that substantially higher levels of CAV1 were present in endometrial tumors than the normal proliferative epithelium. Also, in Ishikawa and Hec-1A endometrial cancer cells CAV1 expression was readily detectable. Upon treatment with 4-TPA CAV1 levels increased and coincided with augmented cell transmigration, matrigel invasion, as well as colony formation in soft agar. Reduction of CAV1 expression using short-hairpin RNA constructs ablated these effects in both cell types whether treated or not with 4-TPA. Alternatively, CAV1 expression appeared not to modulate significantly proliferation of these cells.Our study shows that elevated CAV1, observed in patients with endometrial cancer, is linked to enhanced malignancy of endometrial cancer cells, as evidenced by increased migration, invasion and anchorage-independent growth.


PubMed | Institute of Biomedical science ICBM, University of Talca, University of Santiago de Chile and Advanced Center for Chronic Diseases iS
Type: | Journal: Molecular cancer | Year: 2015

Survivin, a member of the inhibitor of apoptosis family of proteins (IAPs) that controls cell division, apoptosis, metastasis and angiogenesis, is overexpressed in essentially all human cancers. As a consequence, the gene/protein is considered an attractive target for cancer treatment. Here, we discuss recent findings related to the regulation of survivin expression and its role in angiogenesis, particularly in the context of hypoxia. We propose a novel role for survivin in cancer, whereby expression of the protein in tumor cells promotes VEGF synthesis, secretion and angiogenesis. Mechanistically, we propose the existence of a positive feed-back loop involving PI3-kinase/Akt activation and enhanced -Catenin-TCF/LEF-dependent VEGF expression followed by secretion. Finally, we elaborate on the possibility that this mechanism operating in cancer cells may contribute to enhanced tumor vascularization by vasculogenic mimicry together with conventional angiogenesis.

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