Selene Elifio Esposito | Pontifícia Universidade Católica do Paraná (original) (raw)

Papers by Selene Elifio Esposito

Research paper thumbnail of Marine Actinomycetes-Derived Secondary Metabolites Overcome TRAIL-Resistance via the Intrinsic Pathway through Downregulation of Survivin and XIAP

Cells

Resistance of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-ind... more Resistance of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis represents the major hurdle to the clinical use of TRAIL or its derivatives. The discovery and development of lead compounds able to sensitize tumor cells to TRAIL-induced cell death is thus likely to overcome this limitation. We recently reported that marine actinomycetes’ crude extracts could restore TRAIL sensitivity of the MDA-MB-231 resistant triple negative breast cancer cell line. We demonstrate in this study, that purified secondary metabolites originating from distinct marine actinomycetes (sharkquinone (1), resistomycin (2), undecylprodigiosin (3), butylcyclopentylprodigiosin (4), elloxizanone A (5) and B (6), carboxyexfoliazone (7), and exfoliazone (8)), alone, and in a concentration-dependent manner, induce killing in both MDA-MB-231 and HCT116 cell lines. Combined with TRAIL, these compounds displayed additive to synergistic apoptotic activity in the Jurkat, H...

Research paper thumbnail of Crystallinity of TiO2 nanotubes and its effects on fibroblast viability, adhesion, and proliferation

Journal of Materials Science: Materials in Medicine

Research paper thumbnail of An overview of neuroblastoma cell lineage phenotypes and in vitro models

Experimental Biology and Medicine

This review was conducted to present the main neuroblastoma (NB) clinical characteristics and the... more This review was conducted to present the main neuroblastoma (NB) clinical characteristics and the most common genetic alterations present in these pediatric tumors, highlighting their impact in tumor cell aggressiveness behavior, including metastatic development and treatment resistance, and patients’ prognosis. The distinct three NB cell lineage phenotypes, S-type, N-type, and I-type, which are characterized by unique cell surface markers and gene expression patterns, are also reviewed. Finally, an overview of the most used NB cell lines currently available for in vitro studies and their unique cellular and molecular characteristics, which should be taken into account for the selection of the most appropriate model for NB pre-clinical studies, is presented. These valuable models can be complemented by the generation of NB reprogrammed tumor cells or organoids, derived directly from patients’ tumor specimens, in the direction toward personalized medicine. Impact statement This revie...

Research paper thumbnail of Influence of selective laser sintering process parameters on microstructure and physicochemical properties of poly(vinyl alcohol) for the production of scaffolds

Rapid Prototyping Journal

Purpose This study aims to investigate the production of scaffolds by selective laser sintering (... more Purpose This study aims to investigate the production of scaffolds by selective laser sintering (SLS) using poly(vinyl alcohol) (PVA) polymer, for in vitro studies, a relatively new and growing area in which scaffolds could be used in the design of three-dimensional models for in vitro disease model or tissue equivalent for safety and effectiveness tests. Design/methodology/approach The influence of the SLS process parameters laser power, 26 W and 32 W, and number of laser scans, 1, 2, 4 and 6, on the surface microstructure of the samples and on the degree of crystallinity and chemical stability of PVA material, was investigated using powder with particle size of 20-320 µm. Laser sintered PVA samples were subjected to cell culture tests using osteoblastic cells derived from human osteosarcoma (SaOs-2). Findings The laser power has no significant influence on the microstructure of the laser-sintered samples, however the number of scans has a considerable influence on the sintering de...

Research paper thumbnail of A comprehensive analysis of AHRR gene as a candidate for cleft lip with or without cleft palate

Mutation Research/Reviews in Mutation Research

Research paper thumbnail of Intradermal injection of Bothrops cotiara venom in mice in an experimental wound model

Journal of Venomous Animals and Toxins including Tropical Diseases

Bothropic envenomation induces hemorrhage, coagulant disturbances and necrosis. Regarding therapi... more Bothropic envenomation induces hemorrhage, coagulant disturbances and necrosis. Regarding therapies against the local damage caused by the venom, there is little information on tissue changes until the complete healing. In the current study, local damage was evaluated by examination of morphological inflammatory alterations, mast cell count, and analysis of collagen deposition. Bleeding was evident four hours after inoculation. After 24 hours, a large area of injury appeared presenting disorganized tissue, significant hemorrhage and acute inflammation. After three days, the damaged area was extensive, with a large amount of inflammatory cells and the presence of scab. In seven days, healing and reepithelization process started. And, 21 days later, the epithelium showed less infiltration and no skin appendages. The number of mast cells was similar to control after four hours, with a drop of 50% at 24 hours, followed by an increase until the 21 st day. No differences of collagen deposition were observed among experimental groups. Taken together, wound healing after intradermal injection of Bothrops cotiara venom in mice follows similar parameters to wounds caused by other bothropic venoms. The present work reveals the importance of experimental wound models to the study of neutralizing agents against venom toxins.

Research paper thumbnail of Análise De Parâmetros Bioquímicos Do Sangue De Camundongos Tratados Com Lidocaína

Estudos de Biologia

Estudos anteriores sobre os efeitos colaterais da Lidocaína mostraram que ao ser administrada cro... more Estudos anteriores sobre os efeitos colaterais da Lidocaína mostraram que ao ser administrada cronicamente em camundongos, causava lesões nos rins e no fígado. Neste trabalho, avaliou-se, por meio de testes bioquímicos (Bilirrubina, Transaminase Pirúvica -TGP, Transaminase Oxalacética - TGO e Creatinina), a hepatotoxicidade e a nefrotoxicidade do anestésico. Em nossas condições experimentais e, após administrações diárias durante 14 dias, não se observaram alterações significativas em tais marcadores bioquímicos plasmáticos.

Research paper thumbnail of Effect of crystalline phases of titania nanotube arrays on adipose derived stem cell adhesion and proliferation

Materials Science and Engineering: C

Research paper thumbnail of Abstract A14: Copy number profiling in South African breast cancer patients

Research paper thumbnail of Selective Laser Sintering of poly(vinyl alcohol) with the purpose of producing scaffolds for in vitro studies

Procceedings of the 24th ABCM International Congress of Mechanical Engineering

Research paper thumbnail of Cancer stem cell markers ALDH1 and CD44+/CD24- phenotype and their prognosis impact in invasive ductal carcinoma

European Journal of Histochemistry

Breast cancer is a very heterogeneous disease. The intrinsic molecular subtypes can explain the i... more Breast cancer is a very heterogeneous disease. The intrinsic molecular subtypes can explain the intertumoral heterogeneity and the cancer stem cell (CSC) hypothesis can explain the intratumoral heterogeneity of this kind of tumor. CD44+/CD24- phenotype and ALDH1 expression are the major CSC markers described in invasive breast cancer. In the present study, 144 samples of invasive breast carcinoma, no special type were distributed in 15 tissue microarrays (TMA) and then evaluated for expression of the CD44+/CD24- phenotype and ALDH1 to understand the importance of these CSC markers and the clinical aspects of breast cancer. The samples were classified into four molecular subtypes according to clinicopathological criteria: Luminal A, Luminal B, HER2, and Basal-like. A statistical association was found between the molecular subtypes and the CSC markers, with HER2 the most frequent subtype for both markers. ALDH1 was also associated with other poor prognostic variables, such as a high h...

Research paper thumbnail of Antitumoral effects of Amblyomma sculptum Berlese saliva in neuroblastoma cell lines involve cytoskeletal deconstruction and cell cycle arrest

Revista Brasileira de Parasitologia Veterinária

The antitumor properties of ticks salivary gland extracts or recombinant proteins have been repor... more The antitumor properties of ticks salivary gland extracts or recombinant proteins have been reported recently, but little is known about the antitumor properties of the secreted components of saliva. The goal of this study was to investigate the in vitro effect of the saliva of the hard tick Amblyomma sculptum on neuroblastoma cell lines. SK-N-SK, SH-SY5Y, Be(2)-M17, IMR-32, and CHLA-20 cells were susceptible to saliva, with 80% reduction in their viability compared to untreated controls, as demonstrated by the methylene blue assay. Further investigation using CHLA-20 revealed apoptosis, with approximately 30% of annexin-V positive cells, and G0/G1-phase accumulation (>60%) after treatment with saliva. Mitochondrial membrane potential (Δψm) was slightly, but significantly (p < 0.05), reduced and the actin cytoskeleton was disarranged, as indicated by fluorescent microscopy. The viability of human fibroblast (HFF-1 cells) used as a non-tumoral control decreased by approximately...

Research paper thumbnail of Effects of calcium and phosphorus incorporation on the properties and bioactivity of TiO2 nanotubes

Journal of Biomaterials Applications

In this study, we investigate the formation of calcium and phosphorus-doped TiO2 nanotubes, produ... more In this study, we investigate the formation of calcium and phosphorus-doped TiO2 nanotubes, produced by potentiostatic anodization of Ti in viscous electrolyte-containing HF and Ca/P ions. Characterization of the produced oxide layer was conducted using scanning electron microscopy, glancing-angle X-ray diffraction, X-ray photoelectron spectroscopy, contact angle, and protein adsorption measurements. Adipose-derived stem cells were used to study material cytotoxicity, cell viability and proliferation, and cell morphology and growth. To evaluate the adipose-derived stem-cell differentiation, we investigated the expression of osteocalcin and osteopontin by cells as well as calcium mineralization. Results show that it was possible to produce a superhydrophilic titanium oxide nanotube layer with incorporation of Ca and P ions. The presence of Ca and P in the oxide layer not only improved the cell adhesion and proliferation but also stimulated the production of key marker proteins indica...

Research paper thumbnail of Patterns of copy number alterations in primary breast tumors of South African patients and their impact on functional cellular pathways

International journal of oncology, Jan 10, 2018

Breast cancer is the most common and the leading cause of female mortality among South African (S... more Breast cancer is the most common and the leading cause of female mortality among South African (SA) women. Several non‑biological and biological risk factors may be attributed to their observed high mortality rate; however, the molecular profiles associated with their breast tumors are poorly characterized. The present study examined the patterns of genome-wide copy number alterations (CNAs) and their potential impact on functional cellular pathways targeted by cancer driver genes in patients with breast cancer from the Western Cape region of SA. Array-comparative genomic hybridization analysis, performed in 28 cases of invasive breast cancer, revealed a mean number of 8.68±6.18 CNAs per case, affecting primarily the Xp22.3 and 6p21-p25 cytobands (57.14% of the cases), followed by 19p13.3-p13.11 (35.7%), 2p25.3-p24.3, 4p16.3-p15.3, 8q11.1-q24.3 and 16 p13.3-p11.2 (32.14%). Functional enrichment analysis of genes and microRNA targets mapped in these affected cytobands revealed critic...

Research paper thumbnail of Abstract 5822: Increase in protein expression and copy number drives the activation of NPY/Y5R pro-survival loop in chemotherapy-treated neuroblastoma

Research paper thumbnail of Abstract 1465: Regulatory role of miRNA-661 in triple-negative breast cancer of African American women

Research paper thumbnail of p-Cresyl sulfate affects the oxidative burst, phagocytosis process, and antigen presentation of monocyte-derived macrophages

Research paper thumbnail of Effect of Donepezil, Tacrine, Galantamine and Rivastigmine on Acetylcholinesterase Inhibition in Dugesia tigrina

Molecules (Basel, Switzerland), Jan 11, 2016

Dugesia tigrina is a non-parasitic platyhelminth, which has been recently utilized in pharmacolog... more Dugesia tigrina is a non-parasitic platyhelminth, which has been recently utilized in pharmacological models, regarding the nervous system, as it presents a wide sensitivity to drugs. Our trials aimed to propose a model for an in vivo screening of substances with inhibitory activity of the enzyme acetylcholinesterase. Trials were performed with four drugs commercialized in Brazil: donepezil, tacrine, galantamine and rivastigmine, utilized in the control of Alzheimer's disease, to inhibit the activity of acetylcholinesterase. We tested five concentrations of the drugs, with an exposure of 24 h, and the mortality and the inhibition of acetylcholinesterase planarian seizure-like activity (pSLA) and planarian locomotor velocity (pLMV) were measured. Galantamine showed high anticholinesterasic activity when compared to the other drugs, with a reduction of 0.05 μmol·min(-1) and 63% of convulsant activity, presenting screw-like movement and hypokinesia, with pLMV of 65 crossed lines du...

Research paper thumbnail of A C-type lectin from Bothrops jararacussu venom can adhere to extracellular matrix proteins and induce the rolling of leukocytes

Journal of Venomous Animals and Toxins including Tropical Diseases, 2007

Purification of a lectin from Bothrops jararacussu venom (BjcuL) was carried out using agarose-D-... more Purification of a lectin from Bothrops jararacussu venom (BjcuL) was carried out using agarose-D-galactose affinity gel. MALDI-TOF gave a major signal at m/z 32028, suggesting the presence of a dimmer composed of two identical subunits. Divalent cations were required for the lectin activity, as complete absence of such ions reduced hemagglutination. BjcuL was more effective at neutral pH and showed total loss of activity at pH values below 4.0 and above 9.0. Its agglutinating activity remained stable at 25°C until 60min, but increased when at 35°C for at least 15min. Adhesion assays to extracellular matrix (ECM) glycoproteins showed that the biotinylated lectin (0.039-5.0µg/100μl) was capable of binding to fibronectin and vitronectin in a dose-dependent manner. The binding was partially inhibited in the presence of D-galactose. BjcuL (1.25-10μg/30μl) potential was investigated for leukocyte rolling and adhesion to endothelial cells in living microvessels using intravital microscopy, which showed that it induced a dose-dependent increase in rolling and adherence of leukocytes, acting directly on endothelial cells of postcapillary venules. The specific association between lectins and their ligands, either on the cell surface or on the ECM, is related to a variety of biological processes. The complementary characterization of BjcuL, shown here, is useful to further understand the venom effects and as a background for future investigation for therapeutic strategies.

Research paper thumbnail of Human neutrophil migration and activation by BJcuL, a galactose binding lectin purified from Bothrops jararacussu venom

Background: Neutrophil migration to an inflamed site constitutes the first line of the innate imm... more Background: Neutrophil migration to an inflamed site constitutes the first line of the innate immune response against invading microorganisms. Given the crucial role of endogenous lectins in neutrophil mobilization and activation, lectins from exogenous sources have often been considered as putative modulators of leukocyte function. Lectins purified from snake venom have been described as galactoside ligands that induce erythrocyte agglutination and platelet aggregation. This study evaluated human neutrophil migration and activation by C-type lectin BJcuL purified from Bothrops jararacussu venom. Results: Utilizing fluorescence microscopy, we observed that biotinylated-BJcuL was evenly distributed on the neutrophil surface, selectively inhibited by D-galactose. Lectin was able to induce modification in the neutrophil morphology in a spherical shape for a polarized observed by optical microscopy and exposure to BJcuL in a Boyden chamber assay resulted in cell migration. After 30 minutes of incubation with BJcuL we found enhanced neutrophil functions, such as respiratory burst, zymozan phagocytosis and an increase in lissosomal volume. In addition, BJcuL delays late apoptosis neutrophils. Conclusion: These results demonstrate that BJcuL can be implicated in a wide variety of immunological functions including first-line defense against pathogens, cell trafficking and induction of the innate immune response since lectin was capable of inducing potent neutrophil activation.

Research paper thumbnail of Marine Actinomycetes-Derived Secondary Metabolites Overcome TRAIL-Resistance via the Intrinsic Pathway through Downregulation of Survivin and XIAP

Cells

Resistance of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-ind... more Resistance of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis represents the major hurdle to the clinical use of TRAIL or its derivatives. The discovery and development of lead compounds able to sensitize tumor cells to TRAIL-induced cell death is thus likely to overcome this limitation. We recently reported that marine actinomycetes’ crude extracts could restore TRAIL sensitivity of the MDA-MB-231 resistant triple negative breast cancer cell line. We demonstrate in this study, that purified secondary metabolites originating from distinct marine actinomycetes (sharkquinone (1), resistomycin (2), undecylprodigiosin (3), butylcyclopentylprodigiosin (4), elloxizanone A (5) and B (6), carboxyexfoliazone (7), and exfoliazone (8)), alone, and in a concentration-dependent manner, induce killing in both MDA-MB-231 and HCT116 cell lines. Combined with TRAIL, these compounds displayed additive to synergistic apoptotic activity in the Jurkat, H...

Research paper thumbnail of Crystallinity of TiO2 nanotubes and its effects on fibroblast viability, adhesion, and proliferation

Journal of Materials Science: Materials in Medicine

Research paper thumbnail of An overview of neuroblastoma cell lineage phenotypes and in vitro models

Experimental Biology and Medicine

This review was conducted to present the main neuroblastoma (NB) clinical characteristics and the... more This review was conducted to present the main neuroblastoma (NB) clinical characteristics and the most common genetic alterations present in these pediatric tumors, highlighting their impact in tumor cell aggressiveness behavior, including metastatic development and treatment resistance, and patients’ prognosis. The distinct three NB cell lineage phenotypes, S-type, N-type, and I-type, which are characterized by unique cell surface markers and gene expression patterns, are also reviewed. Finally, an overview of the most used NB cell lines currently available for in vitro studies and their unique cellular and molecular characteristics, which should be taken into account for the selection of the most appropriate model for NB pre-clinical studies, is presented. These valuable models can be complemented by the generation of NB reprogrammed tumor cells or organoids, derived directly from patients’ tumor specimens, in the direction toward personalized medicine. Impact statement This revie...

Research paper thumbnail of Influence of selective laser sintering process parameters on microstructure and physicochemical properties of poly(vinyl alcohol) for the production of scaffolds

Rapid Prototyping Journal

Purpose This study aims to investigate the production of scaffolds by selective laser sintering (... more Purpose This study aims to investigate the production of scaffolds by selective laser sintering (SLS) using poly(vinyl alcohol) (PVA) polymer, for in vitro studies, a relatively new and growing area in which scaffolds could be used in the design of three-dimensional models for in vitro disease model or tissue equivalent for safety and effectiveness tests. Design/methodology/approach The influence of the SLS process parameters laser power, 26 W and 32 W, and number of laser scans, 1, 2, 4 and 6, on the surface microstructure of the samples and on the degree of crystallinity and chemical stability of PVA material, was investigated using powder with particle size of 20-320 µm. Laser sintered PVA samples were subjected to cell culture tests using osteoblastic cells derived from human osteosarcoma (SaOs-2). Findings The laser power has no significant influence on the microstructure of the laser-sintered samples, however the number of scans has a considerable influence on the sintering de...

Research paper thumbnail of A comprehensive analysis of AHRR gene as a candidate for cleft lip with or without cleft palate

Mutation Research/Reviews in Mutation Research

Research paper thumbnail of Intradermal injection of Bothrops cotiara venom in mice in an experimental wound model

Journal of Venomous Animals and Toxins including Tropical Diseases

Bothropic envenomation induces hemorrhage, coagulant disturbances and necrosis. Regarding therapi... more Bothropic envenomation induces hemorrhage, coagulant disturbances and necrosis. Regarding therapies against the local damage caused by the venom, there is little information on tissue changes until the complete healing. In the current study, local damage was evaluated by examination of morphological inflammatory alterations, mast cell count, and analysis of collagen deposition. Bleeding was evident four hours after inoculation. After 24 hours, a large area of injury appeared presenting disorganized tissue, significant hemorrhage and acute inflammation. After three days, the damaged area was extensive, with a large amount of inflammatory cells and the presence of scab. In seven days, healing and reepithelization process started. And, 21 days later, the epithelium showed less infiltration and no skin appendages. The number of mast cells was similar to control after four hours, with a drop of 50% at 24 hours, followed by an increase until the 21 st day. No differences of collagen deposition were observed among experimental groups. Taken together, wound healing after intradermal injection of Bothrops cotiara venom in mice follows similar parameters to wounds caused by other bothropic venoms. The present work reveals the importance of experimental wound models to the study of neutralizing agents against venom toxins.

Research paper thumbnail of Análise De Parâmetros Bioquímicos Do Sangue De Camundongos Tratados Com Lidocaína

Estudos de Biologia

Estudos anteriores sobre os efeitos colaterais da Lidocaína mostraram que ao ser administrada cro... more Estudos anteriores sobre os efeitos colaterais da Lidocaína mostraram que ao ser administrada cronicamente em camundongos, causava lesões nos rins e no fígado. Neste trabalho, avaliou-se, por meio de testes bioquímicos (Bilirrubina, Transaminase Pirúvica -TGP, Transaminase Oxalacética - TGO e Creatinina), a hepatotoxicidade e a nefrotoxicidade do anestésico. Em nossas condições experimentais e, após administrações diárias durante 14 dias, não se observaram alterações significativas em tais marcadores bioquímicos plasmáticos.

Research paper thumbnail of Effect of crystalline phases of titania nanotube arrays on adipose derived stem cell adhesion and proliferation

Materials Science and Engineering: C

Research paper thumbnail of Abstract A14: Copy number profiling in South African breast cancer patients

Research paper thumbnail of Selective Laser Sintering of poly(vinyl alcohol) with the purpose of producing scaffolds for in vitro studies

Procceedings of the 24th ABCM International Congress of Mechanical Engineering

Research paper thumbnail of Cancer stem cell markers ALDH1 and CD44+/CD24- phenotype and their prognosis impact in invasive ductal carcinoma

European Journal of Histochemistry

Breast cancer is a very heterogeneous disease. The intrinsic molecular subtypes can explain the i... more Breast cancer is a very heterogeneous disease. The intrinsic molecular subtypes can explain the intertumoral heterogeneity and the cancer stem cell (CSC) hypothesis can explain the intratumoral heterogeneity of this kind of tumor. CD44+/CD24- phenotype and ALDH1 expression are the major CSC markers described in invasive breast cancer. In the present study, 144 samples of invasive breast carcinoma, no special type were distributed in 15 tissue microarrays (TMA) and then evaluated for expression of the CD44+/CD24- phenotype and ALDH1 to understand the importance of these CSC markers and the clinical aspects of breast cancer. The samples were classified into four molecular subtypes according to clinicopathological criteria: Luminal A, Luminal B, HER2, and Basal-like. A statistical association was found between the molecular subtypes and the CSC markers, with HER2 the most frequent subtype for both markers. ALDH1 was also associated with other poor prognostic variables, such as a high h...

Research paper thumbnail of Antitumoral effects of Amblyomma sculptum Berlese saliva in neuroblastoma cell lines involve cytoskeletal deconstruction and cell cycle arrest

Revista Brasileira de Parasitologia Veterinária

The antitumor properties of ticks salivary gland extracts or recombinant proteins have been repor... more The antitumor properties of ticks salivary gland extracts or recombinant proteins have been reported recently, but little is known about the antitumor properties of the secreted components of saliva. The goal of this study was to investigate the in vitro effect of the saliva of the hard tick Amblyomma sculptum on neuroblastoma cell lines. SK-N-SK, SH-SY5Y, Be(2)-M17, IMR-32, and CHLA-20 cells were susceptible to saliva, with 80% reduction in their viability compared to untreated controls, as demonstrated by the methylene blue assay. Further investigation using CHLA-20 revealed apoptosis, with approximately 30% of annexin-V positive cells, and G0/G1-phase accumulation (>60%) after treatment with saliva. Mitochondrial membrane potential (Δψm) was slightly, but significantly (p < 0.05), reduced and the actin cytoskeleton was disarranged, as indicated by fluorescent microscopy. The viability of human fibroblast (HFF-1 cells) used as a non-tumoral control decreased by approximately...

Research paper thumbnail of Effects of calcium and phosphorus incorporation on the properties and bioactivity of TiO2 nanotubes

Journal of Biomaterials Applications

In this study, we investigate the formation of calcium and phosphorus-doped TiO2 nanotubes, produ... more In this study, we investigate the formation of calcium and phosphorus-doped TiO2 nanotubes, produced by potentiostatic anodization of Ti in viscous electrolyte-containing HF and Ca/P ions. Characterization of the produced oxide layer was conducted using scanning electron microscopy, glancing-angle X-ray diffraction, X-ray photoelectron spectroscopy, contact angle, and protein adsorption measurements. Adipose-derived stem cells were used to study material cytotoxicity, cell viability and proliferation, and cell morphology and growth. To evaluate the adipose-derived stem-cell differentiation, we investigated the expression of osteocalcin and osteopontin by cells as well as calcium mineralization. Results show that it was possible to produce a superhydrophilic titanium oxide nanotube layer with incorporation of Ca and P ions. The presence of Ca and P in the oxide layer not only improved the cell adhesion and proliferation but also stimulated the production of key marker proteins indica...

Research paper thumbnail of Patterns of copy number alterations in primary breast tumors of South African patients and their impact on functional cellular pathways

International journal of oncology, Jan 10, 2018

Breast cancer is the most common and the leading cause of female mortality among South African (S... more Breast cancer is the most common and the leading cause of female mortality among South African (SA) women. Several non‑biological and biological risk factors may be attributed to their observed high mortality rate; however, the molecular profiles associated with their breast tumors are poorly characterized. The present study examined the patterns of genome-wide copy number alterations (CNAs) and their potential impact on functional cellular pathways targeted by cancer driver genes in patients with breast cancer from the Western Cape region of SA. Array-comparative genomic hybridization analysis, performed in 28 cases of invasive breast cancer, revealed a mean number of 8.68±6.18 CNAs per case, affecting primarily the Xp22.3 and 6p21-p25 cytobands (57.14% of the cases), followed by 19p13.3-p13.11 (35.7%), 2p25.3-p24.3, 4p16.3-p15.3, 8q11.1-q24.3 and 16 p13.3-p11.2 (32.14%). Functional enrichment analysis of genes and microRNA targets mapped in these affected cytobands revealed critic...

Research paper thumbnail of Abstract 5822: Increase in protein expression and copy number drives the activation of NPY/Y5R pro-survival loop in chemotherapy-treated neuroblastoma

Research paper thumbnail of Abstract 1465: Regulatory role of miRNA-661 in triple-negative breast cancer of African American women

Research paper thumbnail of p-Cresyl sulfate affects the oxidative burst, phagocytosis process, and antigen presentation of monocyte-derived macrophages

Research paper thumbnail of Effect of Donepezil, Tacrine, Galantamine and Rivastigmine on Acetylcholinesterase Inhibition in Dugesia tigrina

Molecules (Basel, Switzerland), Jan 11, 2016

Dugesia tigrina is a non-parasitic platyhelminth, which has been recently utilized in pharmacolog... more Dugesia tigrina is a non-parasitic platyhelminth, which has been recently utilized in pharmacological models, regarding the nervous system, as it presents a wide sensitivity to drugs. Our trials aimed to propose a model for an in vivo screening of substances with inhibitory activity of the enzyme acetylcholinesterase. Trials were performed with four drugs commercialized in Brazil: donepezil, tacrine, galantamine and rivastigmine, utilized in the control of Alzheimer's disease, to inhibit the activity of acetylcholinesterase. We tested five concentrations of the drugs, with an exposure of 24 h, and the mortality and the inhibition of acetylcholinesterase planarian seizure-like activity (pSLA) and planarian locomotor velocity (pLMV) were measured. Galantamine showed high anticholinesterasic activity when compared to the other drugs, with a reduction of 0.05 μmol·min(-1) and 63% of convulsant activity, presenting screw-like movement and hypokinesia, with pLMV of 65 crossed lines du...

Research paper thumbnail of A C-type lectin from Bothrops jararacussu venom can adhere to extracellular matrix proteins and induce the rolling of leukocytes

Journal of Venomous Animals and Toxins including Tropical Diseases, 2007

Purification of a lectin from Bothrops jararacussu venom (BjcuL) was carried out using agarose-D-... more Purification of a lectin from Bothrops jararacussu venom (BjcuL) was carried out using agarose-D-galactose affinity gel. MALDI-TOF gave a major signal at m/z 32028, suggesting the presence of a dimmer composed of two identical subunits. Divalent cations were required for the lectin activity, as complete absence of such ions reduced hemagglutination. BjcuL was more effective at neutral pH and showed total loss of activity at pH values below 4.0 and above 9.0. Its agglutinating activity remained stable at 25°C until 60min, but increased when at 35°C for at least 15min. Adhesion assays to extracellular matrix (ECM) glycoproteins showed that the biotinylated lectin (0.039-5.0µg/100μl) was capable of binding to fibronectin and vitronectin in a dose-dependent manner. The binding was partially inhibited in the presence of D-galactose. BjcuL (1.25-10μg/30μl) potential was investigated for leukocyte rolling and adhesion to endothelial cells in living microvessels using intravital microscopy, which showed that it induced a dose-dependent increase in rolling and adherence of leukocytes, acting directly on endothelial cells of postcapillary venules. The specific association between lectins and their ligands, either on the cell surface or on the ECM, is related to a variety of biological processes. The complementary characterization of BjcuL, shown here, is useful to further understand the venom effects and as a background for future investigation for therapeutic strategies.

Research paper thumbnail of Human neutrophil migration and activation by BJcuL, a galactose binding lectin purified from Bothrops jararacussu venom

Background: Neutrophil migration to an inflamed site constitutes the first line of the innate imm... more Background: Neutrophil migration to an inflamed site constitutes the first line of the innate immune response against invading microorganisms. Given the crucial role of endogenous lectins in neutrophil mobilization and activation, lectins from exogenous sources have often been considered as putative modulators of leukocyte function. Lectins purified from snake venom have been described as galactoside ligands that induce erythrocyte agglutination and platelet aggregation. This study evaluated human neutrophil migration and activation by C-type lectin BJcuL purified from Bothrops jararacussu venom. Results: Utilizing fluorescence microscopy, we observed that biotinylated-BJcuL was evenly distributed on the neutrophil surface, selectively inhibited by D-galactose. Lectin was able to induce modification in the neutrophil morphology in a spherical shape for a polarized observed by optical microscopy and exposure to BJcuL in a Boyden chamber assay resulted in cell migration. After 30 minutes of incubation with BJcuL we found enhanced neutrophil functions, such as respiratory burst, zymozan phagocytosis and an increase in lissosomal volume. In addition, BJcuL delays late apoptosis neutrophils. Conclusion: These results demonstrate that BJcuL can be implicated in a wide variety of immunological functions including first-line defense against pathogens, cell trafficking and induction of the innate immune response since lectin was capable of inducing potent neutrophil activation.