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Ana Cardoso

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Alexandra Carvalho

Instituto Superior Técnico

University of California, Riverside

Brandon McKenna

University of California, Santa Barbara

Ana Lazaro-carrillo

Rodolfo Miranda

Francisco Sánchez

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Papers by Ana Cardoso

In vitro studies with mammalian cell lines and gum arabic-coated magnetic nanoparticles

Journal of Molecular Recognition, 2010

Iron oxide magnetic nanoparticles (MNPs) were synthesized by the chemical co-precipitation method... more Iron oxide magnetic nanoparticles (MNPs) were synthesized by the chemical co-precipitation method and coated with gum arabic (GA) by physical adsorption and covalent attachment. Cultures of mammalian cell lines (HEK293, CHO and TE671) were grown in the presence of uncoated and GA-coated MNPs. Cellular growth was followed by optical microscopy in order to assess the proportion of cells with particles, alterations in cellular density and the presence of debris. The in vitro assays demonstrated that cells from different origins are affected differently by the presence of the nanoparticles. Also, the methods followed for GA coating of MNPs endow distinct surface characteristics that probably underlie the observed differences when in contact with the cells. In general, the nanoparticles to which the GA was adsorbed had a smaller ability to attach to the cells' surface and to compromise the viability of the cultures.

Biocompatible and bioactive gum Arabic coated iron oxide magnetic nanoparticles

Journal of Biotechnology, 2009

The surface modification of iron oxide magnetic nanoparticles (MNPs) with gum Arabic (GA) via ads... more The surface modification of iron oxide magnetic nanoparticles (MNPs) with gum Arabic (GA) via adsorption and covalent coupling was studied. The adsorption of GA was assessed during MNP chemical synthesis by the co-precipitation method (MNP_GA), and after MNP synthesis on both bare magnetite and MNP_GA. The covalent immobilization of GA at the surface of aldehyde-activated (MNP_GA(APTES)) or aminated MNPs (MNP_GA(EDC)) was achieved through free terminal amino and carboxylate groups from GA. The presence of GA at the surface of the MNPs was confirmed by FTIR and by the quantification of GA by the bicinchoninic acid test. Results indicated that the maximum of GA coating was obtained for the covalent coupling of GA through its free carboxylate groups (MNP_GA(EDC)), yielding a maximum of 1.8g of GA bound/g of dried particles. The hydrodynamic diameter of MNPs modified with GA after synthesis resulted in the lowest values, in opposition to the MNPs co-precipitated with GA which presented the tendency to form larger aggregates of up to 1mum. The zeta potentials indicate the existence of negatively charged surfaces before and after GA coating. The potential of the GA coated MNPs for further biomolecule attachment was assessed through anchorage of a model antibody to aldehyde-functionalized MNP_GA and its subsequent detection with an FITC labeled anti-antibody.

Fragmentation reactions of molecular ions and dications of indoleamines

European Journal of Mass Spectrometry, 1999

Page 1. Fragmentation Reactions of Molecular Ions and Dications of Indoleamines AM Cardoso and AJ... more

Hypolimnetic withdrawal coupled with oxygenation as lake restoration measures: the successful case of Lake Varese (Italy)

Lake Varese is a relatively small lake, belonging to the drainage basin of lake Maggiore (norther... more Lake Varese is a relatively small lake, belonging to the drainage basin of lake Maggiore (northern Italy). It has had a long his- tory (since 1960s) of water quality deterioration as the result of cultural eutrophication. In 1967 a restoration project was designed, including a sewerage network, an O-ring sewage diversion system, and a centralised wastewater treatment plant with phosphorus

Studies of Labor Market Intermediation

Microscopy and Microanalysis of an Extreme Case of Salt and Biodegradation in 17th Century Wall Paintings

Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada, 2015

The present study characterizes the main deterioration mechanisms affecting the early 17th fresco... more The present study characterizes the main deterioration mechanisms affecting the early 17th frescoes of Casa de Fresco, the only known example in Portugal of a semi-underground leisure room richly decorated with a balcony over a water well. Frescoes from the vault are at risk due to salt weathering and biodeterioration. The aim of the research was identification of the deterioration materials, determination of their origin, and their effect on the frescoes before future intervention. Scanning electron microscopy with an energy-dispersive X-ray detector (SEM-EDS) was used to determine salt morphology and microanalysis. The mineralogical characterization was performed by X-ray powder diffraction, complemented with µ-Raman and µ-Fourier transform infrared spectroscopy. Biological assessment was evaluated with optical microscopy and SEM-EDS. Bacterial and fungal isolation and identification were performed using standard culture media and methods according to Bergey's Manual of System...

Factores de la deserción escolar en Brasil. El papel de la paternidad temprana, la mano de obra infantil y la pobreza

This paper aims to identify the major factors that lead to school abandonment in an urban surroun... more This paper aims to identify the major factors that lead to school abandonment in an urban surrounding, namely, the shantytowns of Fortaleza, northeast Brazil. We use an extensive survey addressing risk factors faced by the population in these neighborhoods, which covered both in-school and out-of-school youth of both genders. The role of early parenthood, child labor, and poverty in pushing

Matrix metalloproteases as maestros for the dual role of LPS- and IL-10-stimulated macrophages in cancer cell behaviour

BMC Cancer, 2015

Background: The interactions established between macrophages and cancer cells are largely depende... more Background: The interactions established between macrophages and cancer cells are largely dependent on instructions from the tumour microenvironment. Macrophages may differentiate into populations with distinct inflammatory profiles, but knowledge on their role on cancer cell activities is still very scarce. In this work, we investigated the influence of pro-inflammatory (LPS-stimulated) and anti-inflammatory (IL-10-stimulated) macrophages on gastric and colorectal cancer cell invasion, motility/migration, angiogenesis and proteolysis, and the associated molecular mechanisms. Methods: Following exposure of gastric and colon cancer cell lines to LPS-and IL-10-stimulated human macrophages, either by indirect contact or conditioned media, we analyzed the effect of the different macrophage populations on cancer cell invasion, migration, motility and phosphorylation status of EGFR and several interacting partners. Cancer-cell induced angiogenesis upon the influence of conditioned media from both macrophage populations was assessed using the chick embryo chorioallantoic membrane assay. MMP activities were evaluated by gelatin zymograhy.

An interferon-γ-delivery system based on chitosan/poly(γ-glutamic acid) polyelectrolyte complexes modulates macrophage-derived stimulation of cancer cell invasion in vitro

Acta Biomaterialia, 2015

Macrophages represent a large component of the tumour microenvironment and are described to estab... more Macrophages represent a large component of the tumour microenvironment and are described to establish interactions with cancer cells, playing crucial roles in several stages of cancer progression. The functional plasticity of macrophages upon stimulation from the environment makes them susceptible to the influence of cancer cells and also renders them as promising therapeutic targets. In this work, we describe a drug delivery system to modulate the phenotype of macrophages, converting them from the pro-tumour M2 phenotype to the anti-tumour M1 phenotype, based on the incorporation of a pro-inflammatory cytokine (interferon-γ) in chitosan (Ch)/poly(γ-glutamic acid) (γ-PGA) complexes. Ch is a biocompatible cationic polysaccharide extensively studied and γ-PGA is a biodegradable, hydrophilic and negatively charged poly-amino acid. These components interact electrostatically, due to opposite charges, resulting in self-assembled structures that can be designed to deliver active molecules such as drugs and proteins. Ch and γ-PGA were self-assembled into polyelectrolyte multilayer films (PEMs) of 371nm thickness, using the layer-by-layer method. Interferon-γ (IFN-γ) was incorporated within the Ch layers at 100 and 500ng/mL. Ch/γ-PGA PEMs with IFN-γ were able to modulate the phenotype of IL-10-treated macrophages at the cell cytoskeleton and cytokine profile levels, inducing an increase of IL-6 and a decrease of IL-10 production. More interestingly, the pro-invasive role of IL-10-treated macrophages was hindered, as their stimulation of gastric cancer cell invasion in vitro decreased from 4 to 2-fold, upon modulation by Ch/γ-PGA PEMs with IFN-γ. This is the first report proposing Ch/γ-PGA PEMs as a suitable strategy to incorporate and release bioactive IFN-γ with the aim of modulating macrophage phenotype, counteracting their stimulating role on gastric cancer cell invasion.

223 Silencing of survivin enhances the sensitivity of cancer cells to chemotherapeutic agents

European Journal of Cancer Supplements, 2010

Quadros de Pessoal

366: The role of tumour derived extracellular matrices on macrophage polarization

European Journal of Cancer, 2014

splicing products of the ING1 gene affect apoptosis and cell senescence, but the mechanisms are c... more splicing products of the ING1 gene affect apoptosis and cell senescence, but the mechanisms are currently unclear. Materials and Methods: Primary diploid fibroblasts were examined for their propensity to express different isoforms of ING1, and their response to increased and decreased levels of ING1 was examined. Results: Expression of the alternatively spliced ING1a tumor suppressor increases >10-fold during replicative senescence. ING1a overexpression inhibits growth; induces a large flattened cell morphology and the expression of senescence-associated b-galactosidase; increases Rb, p16, and cyclin D1 levels; and results in the accumulation of senescence-associated heterochromatic foci. Here we identify ING1a-regulated genes and find that ING1a induces the expression of a disproportionate number of genes whose products encode proteins involved in endocytosis. Intersectin 2 (ITSN2) is most affected by ING1a, being rapidly induced >25-fold. Overexpression of ITSN2 independently induces expression of the p16 and p57 KIP2 cyclin-dependent kinase inhibitors, which act to block Rb inactivation, acting as downstream effectors of ING1a. ITSN2 is also induced in normally senescing cells, consistent with elevated levels of ING1a inducing ITSN2 as part of a normal senescence program. Inhibition of endocytosis or altering the stoichiometry of endosome components such as Rab family members similarly induces senescence. Knockdown of ITSN2 also blocks the ability of ING1a to induce a senescent phenotype, confirming that ITSN2 is a major transducer of ING1ainduced senescence signaling. Conclusions: These data identify a pathway by which ING1a induces senescence and indicate that altered endocytosis activates the Rb pathway, subsequently effecting a senescent phenotype. Since ING1a levels increase naturally near the end of cell replicative activity, the alternative splicing of ING1 might represent a regulatory event that subsequently prevents senescing cells from responding normally to mitogenic factors, helping enforce the senescence phenotype believed to block the progression of cancer.

Proton affinities of phenylalkylamines by the kinetic method

International Journal of Mass Spectrometry and Ion Processes, 1998

The kinetic method was used to determine the proton affinities of phenylalkylamines of general fo... more The kinetic method was used to determine the proton affinities of phenylalkylamines of general formula RIR2C6H3CHR3(CH2)nNRaR 5 where R ~ = H or OH; R ~ = H, F, NO2, OH or OCH3; R 3 = H or OH; R 4 and R 5 = H and/or CH3; n = 1-3. Amines were used as reference bases and the proton affinities of the phenylalkylamines were bracketed by a pair of reference bases that give rise, in the MIKE spectra of the heterodimer, to more or less intense signals than the compound under study. The influence of the aliphatic chain length and of the substituents on the aromatic ring, on the proton affinities of the phenylalkylamines is presented and discussed. The formation of an hydrogen bond between the amino group and the aromatic ring is proposed to explain the results obtained.

The effect of humidity on the oviposition and larval mortality of Haemaphysalis leporispalustris (Packard, 1869) (Acari: Ixodidae) under laboratory conditions

Revista brasileira de parasitologia veterinária = Brazilian journal of veterinary parasitology : Órgão Oficial do Colégio Brasileiro de Parasitologia Veterinária

Oviposition, reproductive and nutritional efficiency indices (REI and NEI), eclosion and larvae m... more Oviposition, reproductive and nutritional efficiency indices (REI and NEI), eclosion and larvae mortality of Haemaphysalis leporispalustris were studied under controlled conditions, inside desiccators, at constant temperatures of 25+/-1 degrees C and relative humidity (RH) levels adjusted at 30, 50, 70 and 95%. Fourth generation tick specimens, originated from a colony fed on rabbits (Oryctolagus cuniculus), were used. The experiment was conducted between Jul/1999 and Jan/2001. The pre-oviposition and oviposition periods decreased and increased, respectively, according to the increase in RH. The egg mass weight, REI and NEI, increased according to the increase in RH. The females' residual weight, under high humidity levels, was probably small due to a better energetic use for egg production (51.77 +/- 11.06 mg at 95% RH). The incubation period was inversely proportional to RH increase (45.10+/- 2.47 days; 40.33+/- 1.45 days and 36.85+/- 0.37 days at 50% 70% and 95% RH, respectiv...

930: Effect of radiotherapy on macrophages

European Journal of Cancer, 2014

Intermolecular cycloaddition of nonstabilized azomethine ylides generated from 1,3-thiazolidine-4-carboxylic acids: synthesis of 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazoles

Tetrahedron, 2006

The 1,3-dipolar cycloaddition of dimethyl acetylenedicarboxylate with nonstabilized azomethine yl... more The 1,3-dipolar cycloaddition of dimethyl acetylenedicarboxylate with nonstabilized azomethine ylides, generated via the decarboxylative condensation of 1,3-thiazolidine-4-carboxylic acids with aldehydes, afforded 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazole derivatives. 2-Substituted-1,3-thiazolidine-4-carboxylic acids led to the stereoselective formation of 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazoles. Quantum-chemistry calculations were carried out allowing the rationalization of the observed stereoselective formation of the anti-dipole.

Thermoresponsive hydrogels with low toxicity from mixtures of ethyl(hydroxyethyl) cellulose and arginine-based surfactants

International Journal of Pharmaceutics, 2012

Ethyl(hydroxyethyl) cellulose (EHEC) is known to form hydrogels in water at elevated temperatures... more Ethyl(hydroxyethyl) cellulose (EHEC) is known to form hydrogels in water at elevated temperatures in the presence of an ionic surfactant. In this paper, the potential use of arginine-based surfactants is explored considering the production of a low toxicity thermoresponsive hydrogel for pharmaceutical and biomedical applications. The interactions between EHEC and the monomeric surfactant N ␣ -lauroyll-arginine methyl ester (LAM) and two gemini surfactants N ␣ ,N ω -bis(N ␣ -acylarginine) ␣,ω-dialkyl amides were evaluated by Rheo-Small Angle Light Scattering measurements. The complex viscosity of the systems was dependent on surfactant concentration and temperature. Under specific conditions, soft gels of homogeneous structure were produced. The cloud point (CP) of the EHEC-LAM system varied significantly with surfactant concentration, while only moderate CP changes were found in the presence of the gemini surfactants. Finally, the effect of the surfactants on the viability of a human cell line was evaluated. Despite the lower toxicity of LAM, the superior gel forming efficiency of the gemini surfactants at lower concentrations revealed their advantageous suitability as components of a biocompatible thermoresponsive gel system.

Cell-penetrating peptide-based systems for nucleic acid delivery: A biological and biophysical approach

Methods in Enzymology, 2012

The increasing knowledge on the genetic basis of disease provides a platform for the development ... more The increasing knowledge on the genetic basis of disease provides a platform for the development of promising gene-targeted therapies that can be applied to numerous pathological conditions, including cancer. Such genetic-based approaches involve the use of nucleic acids as therapeutic agents, either for the insertion or for the repair and regulation of specific genes. However, despite the huge pharmacological potential of these molecules, their application remains highly dependent on the development of delivery systems capable of mediating efficient cellular uptake. The discovery of a class of small peptides, the so-called cell-penetrating peptides (CPPs), which are able to very efficiently cross cell membranes through a mechanism that is independent of membrane receptors or transporters and avoids lysosomal enzymatic degradation, has been enthusiastically considered of key interest to improve noninvasive cellular delivery of therapeutic molecules. A large number of CPPs have been applied successfully to mediate the intracellular delivery of nucleic acids, including the S4 13 PV peptide for which interactions with membranes and resulting biological effects are illustrated in this chapter. Here, we provide a description of the experimental procedures for the preparation of CPP-based nucleic acid complexes and assessment of their formation, the selection of those protocols leading to the most efficient complexes, the biophysical characterization of CPP membrane interactions, and the evaluation of the biological and cytotoxic activity of the complexes.

Temporary Agency Work in Portugal, 1995–2000

There is widespread belief that workers in temporary agency work (TAW) are subject to poorer work... more There is widespread belief that workers in temporary agency work (TAW) are subject to poorer working conditions, in particular pay, than comparable workers in the rest of the economy. The first aim of this analysis is to quantify the wage penalty, if any, for workers in TAW. Secondly, we analyze the wage profile of workers before and after spells of

Integration of Different Approaches in Lake Monitoring

Water Quality Measurements, 2000

... periods dependent on satellite orbit and period, and availability of cloud free images High G... more

In vitro studies with mammalian cell lines and gum arabic-coated magnetic nanoparticles

Journal of Molecular Recognition, 2010

Iron oxide magnetic nanoparticles (MNPs) were synthesized by the chemical co-precipitation method... more Iron oxide magnetic nanoparticles (MNPs) were synthesized by the chemical co-precipitation method and coated with gum arabic (GA) by physical adsorption and covalent attachment. Cultures of mammalian cell lines (HEK293, CHO and TE671) were grown in the presence of uncoated and GA-coated MNPs. Cellular growth was followed by optical microscopy in order to assess the proportion of cells with particles, alterations in cellular density and the presence of debris. The in vitro assays demonstrated that cells from different origins are affected differently by the presence of the nanoparticles. Also, the methods followed for GA coating of MNPs endow distinct surface characteristics that probably underlie the observed differences when in contact with the cells. In general, the nanoparticles to which the GA was adsorbed had a smaller ability to attach to the cells' surface and to compromise the viability of the cultures.

Biocompatible and bioactive gum Arabic coated iron oxide magnetic nanoparticles

Journal of Biotechnology, 2009

The surface modification of iron oxide magnetic nanoparticles (MNPs) with gum Arabic (GA) via ads... more The surface modification of iron oxide magnetic nanoparticles (MNPs) with gum Arabic (GA) via adsorption and covalent coupling was studied. The adsorption of GA was assessed during MNP chemical synthesis by the co-precipitation method (MNP_GA), and after MNP synthesis on both bare magnetite and MNP_GA. The covalent immobilization of GA at the surface of aldehyde-activated (MNP_GA(APTES)) or aminated MNPs (MNP_GA(EDC)) was achieved through free terminal amino and carboxylate groups from GA. The presence of GA at the surface of the MNPs was confirmed by FTIR and by the quantification of GA by the bicinchoninic acid test. Results indicated that the maximum of GA coating was obtained for the covalent coupling of GA through its free carboxylate groups (MNP_GA(EDC)), yielding a maximum of 1.8g of GA bound/g of dried particles. The hydrodynamic diameter of MNPs modified with GA after synthesis resulted in the lowest values, in opposition to the MNPs co-precipitated with GA which presented the tendency to form larger aggregates of up to 1mum. The zeta potentials indicate the existence of negatively charged surfaces before and after GA coating. The potential of the GA coated MNPs for further biomolecule attachment was assessed through anchorage of a model antibody to aldehyde-functionalized MNP_GA and its subsequent detection with an FITC labeled anti-antibody.

Fragmentation reactions of molecular ions and dications of indoleamines

European Journal of Mass Spectrometry, 1999

Page 1. Fragmentation Reactions of Molecular Ions and Dications of Indoleamines AM Cardoso and AJ... more

Hypolimnetic withdrawal coupled with oxygenation as lake restoration measures: the successful case of Lake Varese (Italy)

Lake Varese is a relatively small lake, belonging to the drainage basin of lake Maggiore (norther... more Lake Varese is a relatively small lake, belonging to the drainage basin of lake Maggiore (northern Italy). It has had a long his- tory (since 1960s) of water quality deterioration as the result of cultural eutrophication. In 1967 a restoration project was designed, including a sewerage network, an O-ring sewage diversion system, and a centralised wastewater treatment plant with phosphorus

Studies of Labor Market Intermediation

Microscopy and Microanalysis of an Extreme Case of Salt and Biodegradation in 17th Century Wall Paintings

Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada, 2015

The present study characterizes the main deterioration mechanisms affecting the early 17th fresco... more The present study characterizes the main deterioration mechanisms affecting the early 17th frescoes of Casa de Fresco, the only known example in Portugal of a semi-underground leisure room richly decorated with a balcony over a water well. Frescoes from the vault are at risk due to salt weathering and biodeterioration. The aim of the research was identification of the deterioration materials, determination of their origin, and their effect on the frescoes before future intervention. Scanning electron microscopy with an energy-dispersive X-ray detector (SEM-EDS) was used to determine salt morphology and microanalysis. The mineralogical characterization was performed by X-ray powder diffraction, complemented with µ-Raman and µ-Fourier transform infrared spectroscopy. Biological assessment was evaluated with optical microscopy and SEM-EDS. Bacterial and fungal isolation and identification were performed using standard culture media and methods according to Bergey's Manual of System...

Factores de la deserción escolar en Brasil. El papel de la paternidad temprana, la mano de obra infantil y la pobreza

This paper aims to identify the major factors that lead to school abandonment in an urban surroun... more This paper aims to identify the major factors that lead to school abandonment in an urban surrounding, namely, the shantytowns of Fortaleza, northeast Brazil. We use an extensive survey addressing risk factors faced by the population in these neighborhoods, which covered both in-school and out-of-school youth of both genders. The role of early parenthood, child labor, and poverty in pushing

Matrix metalloproteases as maestros for the dual role of LPS- and IL-10-stimulated macrophages in cancer cell behaviour

BMC Cancer, 2015

Background: The interactions established between macrophages and cancer cells are largely depende... more Background: The interactions established between macrophages and cancer cells are largely dependent on instructions from the tumour microenvironment. Macrophages may differentiate into populations with distinct inflammatory profiles, but knowledge on their role on cancer cell activities is still very scarce. In this work, we investigated the influence of pro-inflammatory (LPS-stimulated) and anti-inflammatory (IL-10-stimulated) macrophages on gastric and colorectal cancer cell invasion, motility/migration, angiogenesis and proteolysis, and the associated molecular mechanisms. Methods: Following exposure of gastric and colon cancer cell lines to LPS-and IL-10-stimulated human macrophages, either by indirect contact or conditioned media, we analyzed the effect of the different macrophage populations on cancer cell invasion, migration, motility and phosphorylation status of EGFR and several interacting partners. Cancer-cell induced angiogenesis upon the influence of conditioned media from both macrophage populations was assessed using the chick embryo chorioallantoic membrane assay. MMP activities were evaluated by gelatin zymograhy.

An interferon-γ-delivery system based on chitosan/poly(γ-glutamic acid) polyelectrolyte complexes modulates macrophage-derived stimulation of cancer cell invasion in vitro

Acta Biomaterialia, 2015

Macrophages represent a large component of the tumour microenvironment and are described to estab... more Macrophages represent a large component of the tumour microenvironment and are described to establish interactions with cancer cells, playing crucial roles in several stages of cancer progression. The functional plasticity of macrophages upon stimulation from the environment makes them susceptible to the influence of cancer cells and also renders them as promising therapeutic targets. In this work, we describe a drug delivery system to modulate the phenotype of macrophages, converting them from the pro-tumour M2 phenotype to the anti-tumour M1 phenotype, based on the incorporation of a pro-inflammatory cytokine (interferon-γ) in chitosan (Ch)/poly(γ-glutamic acid) (γ-PGA) complexes. Ch is a biocompatible cationic polysaccharide extensively studied and γ-PGA is a biodegradable, hydrophilic and negatively charged poly-amino acid. These components interact electrostatically, due to opposite charges, resulting in self-assembled structures that can be designed to deliver active molecules such as drugs and proteins. Ch and γ-PGA were self-assembled into polyelectrolyte multilayer films (PEMs) of 371nm thickness, using the layer-by-layer method. Interferon-γ (IFN-γ) was incorporated within the Ch layers at 100 and 500ng/mL. Ch/γ-PGA PEMs with IFN-γ were able to modulate the phenotype of IL-10-treated macrophages at the cell cytoskeleton and cytokine profile levels, inducing an increase of IL-6 and a decrease of IL-10 production. More interestingly, the pro-invasive role of IL-10-treated macrophages was hindered, as their stimulation of gastric cancer cell invasion in vitro decreased from 4 to 2-fold, upon modulation by Ch/γ-PGA PEMs with IFN-γ. This is the first report proposing Ch/γ-PGA PEMs as a suitable strategy to incorporate and release bioactive IFN-γ with the aim of modulating macrophage phenotype, counteracting their stimulating role on gastric cancer cell invasion.

223 Silencing of survivin enhances the sensitivity of cancer cells to chemotherapeutic agents

European Journal of Cancer Supplements, 2010

Quadros de Pessoal

366: The role of tumour derived extracellular matrices on macrophage polarization

European Journal of Cancer, 2014

splicing products of the ING1 gene affect apoptosis and cell senescence, but the mechanisms are c... more splicing products of the ING1 gene affect apoptosis and cell senescence, but the mechanisms are currently unclear. Materials and Methods: Primary diploid fibroblasts were examined for their propensity to express different isoforms of ING1, and their response to increased and decreased levels of ING1 was examined. Results: Expression of the alternatively spliced ING1a tumor suppressor increases >10-fold during replicative senescence. ING1a overexpression inhibits growth; induces a large flattened cell morphology and the expression of senescence-associated b-galactosidase; increases Rb, p16, and cyclin D1 levels; and results in the accumulation of senescence-associated heterochromatic foci. Here we identify ING1a-regulated genes and find that ING1a induces the expression of a disproportionate number of genes whose products encode proteins involved in endocytosis. Intersectin 2 (ITSN2) is most affected by ING1a, being rapidly induced >25-fold. Overexpression of ITSN2 independently induces expression of the p16 and p57 KIP2 cyclin-dependent kinase inhibitors, which act to block Rb inactivation, acting as downstream effectors of ING1a. ITSN2 is also induced in normally senescing cells, consistent with elevated levels of ING1a inducing ITSN2 as part of a normal senescence program. Inhibition of endocytosis or altering the stoichiometry of endosome components such as Rab family members similarly induces senescence. Knockdown of ITSN2 also blocks the ability of ING1a to induce a senescent phenotype, confirming that ITSN2 is a major transducer of ING1ainduced senescence signaling. Conclusions: These data identify a pathway by which ING1a induces senescence and indicate that altered endocytosis activates the Rb pathway, subsequently effecting a senescent phenotype. Since ING1a levels increase naturally near the end of cell replicative activity, the alternative splicing of ING1 might represent a regulatory event that subsequently prevents senescing cells from responding normally to mitogenic factors, helping enforce the senescence phenotype believed to block the progression of cancer.

Proton affinities of phenylalkylamines by the kinetic method

International Journal of Mass Spectrometry and Ion Processes, 1998

The kinetic method was used to determine the proton affinities of phenylalkylamines of general fo... more The kinetic method was used to determine the proton affinities of phenylalkylamines of general formula RIR2C6H3CHR3(CH2)nNRaR 5 where R ~ = H or OH; R ~ = H, F, NO2, OH or OCH3; R 3 = H or OH; R 4 and R 5 = H and/or CH3; n = 1-3. Amines were used as reference bases and the proton affinities of the phenylalkylamines were bracketed by a pair of reference bases that give rise, in the MIKE spectra of the heterodimer, to more or less intense signals than the compound under study. The influence of the aliphatic chain length and of the substituents on the aromatic ring, on the proton affinities of the phenylalkylamines is presented and discussed. The formation of an hydrogen bond between the amino group and the aromatic ring is proposed to explain the results obtained.

The effect of humidity on the oviposition and larval mortality of Haemaphysalis leporispalustris (Packard, 1869) (Acari: Ixodidae) under laboratory conditions

Revista brasileira de parasitologia veterinária = Brazilian journal of veterinary parasitology : Órgão Oficial do Colégio Brasileiro de Parasitologia Veterinária

Oviposition, reproductive and nutritional efficiency indices (REI and NEI), eclosion and larvae m... more Oviposition, reproductive and nutritional efficiency indices (REI and NEI), eclosion and larvae mortality of Haemaphysalis leporispalustris were studied under controlled conditions, inside desiccators, at constant temperatures of 25+/-1 degrees C and relative humidity (RH) levels adjusted at 30, 50, 70 and 95%. Fourth generation tick specimens, originated from a colony fed on rabbits (Oryctolagus cuniculus), were used. The experiment was conducted between Jul/1999 and Jan/2001. The pre-oviposition and oviposition periods decreased and increased, respectively, according to the increase in RH. The egg mass weight, REI and NEI, increased according to the increase in RH. The females' residual weight, under high humidity levels, was probably small due to a better energetic use for egg production (51.77 +/- 11.06 mg at 95% RH). The incubation period was inversely proportional to RH increase (45.10+/- 2.47 days; 40.33+/- 1.45 days and 36.85+/- 0.37 days at 50% 70% and 95% RH, respectiv...

930: Effect of radiotherapy on macrophages

European Journal of Cancer, 2014

Intermolecular cycloaddition of nonstabilized azomethine ylides generated from 1,3-thiazolidine-4-carboxylic acids: synthesis of 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazoles

Tetrahedron, 2006

The 1,3-dipolar cycloaddition of dimethyl acetylenedicarboxylate with nonstabilized azomethine yl... more The 1,3-dipolar cycloaddition of dimethyl acetylenedicarboxylate with nonstabilized azomethine ylides, generated via the decarboxylative condensation of 1,3-thiazolidine-4-carboxylic acids with aldehydes, afforded 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazole derivatives. 2-Substituted-1,3-thiazolidine-4-carboxylic acids led to the stereoselective formation of 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazoles. Quantum-chemistry calculations were carried out allowing the rationalization of the observed stereoselective formation of the anti-dipole.

Thermoresponsive hydrogels with low toxicity from mixtures of ethyl(hydroxyethyl) cellulose and arginine-based surfactants

International Journal of Pharmaceutics, 2012

Ethyl(hydroxyethyl) cellulose (EHEC) is known to form hydrogels in water at elevated temperatures... more Ethyl(hydroxyethyl) cellulose (EHEC) is known to form hydrogels in water at elevated temperatures in the presence of an ionic surfactant. In this paper, the potential use of arginine-based surfactants is explored considering the production of a low toxicity thermoresponsive hydrogel for pharmaceutical and biomedical applications. The interactions between EHEC and the monomeric surfactant N ␣ -lauroyll-arginine methyl ester (LAM) and two gemini surfactants N ␣ ,N ω -bis(N ␣ -acylarginine) ␣,ω-dialkyl amides were evaluated by Rheo-Small Angle Light Scattering measurements. The complex viscosity of the systems was dependent on surfactant concentration and temperature. Under specific conditions, soft gels of homogeneous structure were produced. The cloud point (CP) of the EHEC-LAM system varied significantly with surfactant concentration, while only moderate CP changes were found in the presence of the gemini surfactants. Finally, the effect of the surfactants on the viability of a human cell line was evaluated. Despite the lower toxicity of LAM, the superior gel forming efficiency of the gemini surfactants at lower concentrations revealed their advantageous suitability as components of a biocompatible thermoresponsive gel system.

Cell-penetrating peptide-based systems for nucleic acid delivery: A biological and biophysical approach

Methods in Enzymology, 2012

The increasing knowledge on the genetic basis of disease provides a platform for the development ... more The increasing knowledge on the genetic basis of disease provides a platform for the development of promising gene-targeted therapies that can be applied to numerous pathological conditions, including cancer. Such genetic-based approaches involve the use of nucleic acids as therapeutic agents, either for the insertion or for the repair and regulation of specific genes. However, despite the huge pharmacological potential of these molecules, their application remains highly dependent on the development of delivery systems capable of mediating efficient cellular uptake. The discovery of a class of small peptides, the so-called cell-penetrating peptides (CPPs), which are able to very efficiently cross cell membranes through a mechanism that is independent of membrane receptors or transporters and avoids lysosomal enzymatic degradation, has been enthusiastically considered of key interest to improve noninvasive cellular delivery of therapeutic molecules. A large number of CPPs have been applied successfully to mediate the intracellular delivery of nucleic acids, including the S4 13 PV peptide for which interactions with membranes and resulting biological effects are illustrated in this chapter. Here, we provide a description of the experimental procedures for the preparation of CPP-based nucleic acid complexes and assessment of their formation, the selection of those protocols leading to the most efficient complexes, the biophysical characterization of CPP membrane interactions, and the evaluation of the biological and cytotoxic activity of the complexes.

Temporary Agency Work in Portugal, 1995–2000

There is widespread belief that workers in temporary agency work (TAW) are subject to poorer work... more There is widespread belief that workers in temporary agency work (TAW) are subject to poorer working conditions, in particular pay, than comparable workers in the rest of the economy. The first aim of this analysis is to quantify the wage penalty, if any, for workers in TAW. Secondly, we analyze the wage profile of workers before and after spells of

Integration of Different Approaches in Lake Monitoring

Water Quality Measurements, 2000

... periods dependent on satellite orbit and period, and availability of cloud free images High G... more