Mara de Souza Junqueira
University of São Paulo
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Publication
Featured researches published by Mara de Souza Junqueira.
Inhalation Toxicology | 2010
Kelly Yoshizaki; Johnny Martins de Brito; Alessandra Choqueta de Toledo; N. K. Nakagawa; V. S. Piccin; Mara de Souza Junqueira; Elnara M. Negri; Alessandro Carvalho; A. Ligeiro de Oliveira; W. Tavares de Lima; P. H. Saldiva; Thais Mauad; Mariângela Macchione
Diesel exhaust is the major source of ultrafine particles released during traffic-related pollution. Subjects with chronic respiratory diseases are at greater risk for exacerbations during exposure to air pollution. This study evaluated the effects of subchronic exposure to a low-dose of diesel exhaust particles (DEP). Sixty male BALB/c mice were divided into two groups: (a) Saline: nasal instillation of saline (n = 30); and (b) DEP: nasal instillation of 30 µg of DEP/10 µl of saline (n = 30). Nasal instillations were performed 5 days a week, over 30 and 60 days. Animals were anesthetized with pentobarbital sodium (50 mg/kg intraperitoneal [i.p.]) and sacrificed by exsanguination. Bronchoalveolar lavage (BAL) fluid was performed to evaluate the inflammatory cell count and the concentrations of the interleukin (IL)-4, IL-10, and IL-13 by enzyme-linked immunosorbent assay (ELISA). The gene expression of oligomeric mucus/gel-forming (Muc5ac) was evaluated by real-time polymerase chain reaction (PCR). Histological analysis in the nasal septum and bronchioles was used to evaluate the bronchial and nasal epithelium thickness as well as the acidic and neutral nasal mucus content. The saline group (30 and 60 days) did not show any changes in any of the parameters. However, the instillation of DEP over 60 days increased the expression of Muc5ac in the lungs and the acid mucus content in the nose compared with the 30-day treatment, and it increased the total leukocytes in the BAL and the nasal epithelium thickness compared with saline for 60 days. Cytokines concentrations in the BAL were detectable, with no differences among the groups. Our data suggest that a low-dose of DEP over 60 days induces respiratory tract inflammation.
Environmental Toxicology | 2015
Robson Seriani; Mara de Souza Junqueira; Alessandra Choqueta de Toledo; Milton A. Martins; Marcelo Martins Seckler; Adriano M. Alencar; Elnara M. Negri; Luiz Fernando Ferraz da Silva; Thais Mauad; Paulo Hilário Nascimento Saldiva; Mariangela Macchione
Particulate matter from diesel exhaust (DEP) has toxic properties and can activate intracellular signaling pathways and induce metabolic changes. This study was conducted to evaluate the activation of extracellular signal‐regulated kinase (ERK) and c‐Jun N‐terminal kinase (JNK) and to analyze the mucin profile (acid (AB+), neutral (PAS+), or mixed (AB/PAS+) mucus) and vacuolization (V) of tracheal explants after treatment with 50 or 100 μg/mL DEP for 30 or 60 min. Western blot analyses showed small increases in ERK1/2 and JNK phosphorylation after 30 min of 100 μg/mL DEP treatment compared with the control. An increase in JNK phosphorylation was observed after 60 min of treatment with 50 μg/mL DEP compared with the control. We did not observe any change in the level of ERK1/2 phosphorylation after treatment with 50 μg/mL DEP. Other groups of tracheas were subjected to histological sectioning and stained with periodic acid‐Schiff (PAS) reagent and Alcian Blue (AB). The stained tissue sections were then subjected to morphometric analysis. The results obtained were compared using ANOVA. Treatment with 50 μg/mL DEP for 30 min or 60 min showed a significant increase (p < 0.001) in the amount of acid mucus, a reduction in neutral mucus, a significant reduction in mixed mucus, and greater vacuolization. Our results suggest that compounds found in DEPs are able to activate acid mucus production and enhance vacuolization and cell signaling pathways, which can lead to airway diseases.
Leukemia Research | 2010
Simone V. da Costa; Rosimeire Aparecida Roela; Mara de Souza Junqueira; Camila Arantes; M. Mitzi Brentani
Stromal cells from pediatric myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) associated with MDS (MDS-AML) present high expression of leukemia inhibitor factor (LIF). We demonstrated using mitogen-activated protein kinase (MAPK) inhibitors that in stromal cells from pediatric MDS and MDS-AML, p38MAPK was critical in serum-induced secretion of LIF. The serum induction of phosphorylated p38MAPK form was observed only in stromal cells from healthy children, whereas in MDS and MDS-AML basal levels were maintained suggesting constitutive p38MAPK activation. Our study suggested the possible importance in pediatric MDS of p38MAPK signaling pathway which may be a future therapeutic target.
Journal of Toxicology and Environmental Health | 2015
Robson Seriani; Mara de Souza Junqueira; Alessandra Choqueta de Toledo; Aristides T. Corrêa; Luiz Fernando Ferraz da Silva; Milton A. Martins; Paulo Hilário Nascimento Saldiva; Thais Mauad; Mariângela Macchione
Diesel exhaust particles (DEP) contain organic and inorganic elements that produce damage to the respiratory epithelium. The aim of this study was to determine the mucus profile of tracheal explants exposed to either crude diesel exhaust particles (DEP) or DEP treated with nitric acid (DEP/NA), with hexane (DEP/HEX), or with methanol (DEP/MET) at concentrations of 50 and 100 μg/ml for 30 and 60 min. Tracheal explants were subjected to morphometric analyses to study acidic (AB+), neutral (PAS+), and mixed (AB+/PAS+) mucus production and vacuolization (V). Incubation with 50 μg/ml crude DEP resulted in a rise in acid mucus production, an increase in vacuolization at 30 min, and reduction in neutral mucus at 30 and 60 min. Tracheas exposed to DEP/MET at 50 μg/ml for 30 or 60 min resulted in a significant decrease in neutral mucus production and an elevation in acid mucus production. DEP/HEX increased vacuolization at both 50 and 100 μg/ml at 30 and 60 min of exposure. Treatment with 50 μg/ml for 30 or 60 min significantly elevated mixed mucus levels. These results suggest that DEP appear to be more toxic when administered in combination with HEX or MET. DEP/MET modified the mucus profile of the epithelium, while DEP/HEX altered mucus extrusion, and these responses might be due to bioavailability of individual elements in DEP fractions.
OncoTargets and Therapy | 2016
Michelle Alvares Sarcinelli; Marta de Souza Albernaz; Marzena Szwed; Alexandre Iscaife; Katia R. M. Leite; Mara de Souza Junqueira; Emerson Soares Bernardes; Emerson Oliveira da Silva; Maria Inês Bruno Tavares; Ralph Santos-Oliveira
Monoclonal antibodies as polymeric nanoparticles are quite interesting and endow this new drug category with many advantages, especially by reducing the number of adverse reactions and, in the case of radiopharmaceuticals, also reducing the amount of radiation (dose) administered to the patient. In this study, a nanoradiopharmaceutical was developed using polylactic acid (PLA)/polyvinyl alcohol (PVA)/montmorillonite (MMT)/trastuzumab nanoparticles labeled with technetium-99m (99mTc) for breast cancer imaging. In order to confirm the nanoparticle formation, atomic force microscopy and dynamic light scattering were performed. Cytotoxicity of the nanoparticle and biodistribution with 99mTc in healthy and inducted animals were also measured. The results from atomic force microscopy showed that the nanoparticles were spherical, with a size range of ~200–500 nm. The dynamic light scattering analysis demonstrated that over 90% of the nanoparticles produced had a size of 287 nm with a zeta potential of −14,6 mV. The cytotoxicity results demonstrated that the nanoparticles were capable of reaching breast cancer cells. The biodistribution data demonstrated that the PLA/PVA/MMT/trastuzumab nanoparticles labeled with 99mTc have great renal clearance and also a high uptake by the lesion, as ~45% of the PLA/PVA/MMT/trastuzumab nanoparticles injected were taken up by the lesion. The data support PLA/PVA/MMT/trastuzumab labeled with 99mTc nanoparticles as nanoradiopharmaceuticals for breast cancer imaging.
Oncotarget | 2016
Sofia Nascimento dos Santos; Mara de Souza Junqueira; Guilherme Francisco; Manuel Vilanova; Ana Magalhães; Marcelo Dias Baruffi; Roger Chammas; Adrian L. Harris; Celso A. Reis; Emerson Soares Bernardes
ST6GalNAc-I, the sialyltransferase responsible for sialyl-Tn (sTn) synthesis, has been previously reported to be positively associated with cancer aggressiveness. Here we describe a novel sTn-dependent mechanism for chemotherapeutic resistance. We show that sTn protects cancer cells against chemotherapeutic-induced cell death by decreasing the interaction of cell surface glycan receptors with galectin-3 and increasing its intracellular accumulation. Moreover, exogenously added galectin-3 potentiated the chemotherapeutics-induced cytotoxicity in sTn non-expressing cells, while sTn overexpressing cells were protected. We also found that the expression of sTn was associated with a reduction in galectin-3-binding sites in human gastric samples tumors. ST6GalNAc-I knockdown restored galectin-3-binding sites on the cell surface and chemotherapeutics sensibility. Our results clearly demonstrate that an interruption of O-glycans extension caused by ST6GalNAc-I enzymatic activity leads to tumor cells resistance to chemotherapeutic drugs, highlighting the need for the development of novel strategies to target galectin-3 and/or ST6GalNAc-I.
Experimental and Toxicologic Pathology | 2015
Robson Seriani; Mara de Souza Junqueira; Claudia E. Carvalho-Sousa; Alessandra C.T. Arruda; Diana Martinez; Adriano M. Alencar; Ana L. Garippo; Jôse Mára Brito; Milton A. Martins; Paulo Hilário Nascimento Saldiva; Elnara M. Negri; Thais Mauad; Mariangela Macchione
This study assessed the effects of the diesel exhaust particles on ERK and JNK MAPKs activation, cell rheology (viscoelasticity), and cytotoxicity in bronchial epithelial airway cells (BEAS-2B). Crude DEP and DEP after extraction with hexane (DEP/HEX) were utilized. The partial reduction of some DEP/HEX organics increased the biodisponibility of many metallic elements. JNK and ERK were activated simultaneously by crude DEP with no alterations in viscoelasticity of the cells. Mitochondrial activity, however, revealed a decrease through the MTT assay. DEP/HEX treatment increased viscoelasticity and cytotoxicity (membrane damage), and also activated JNK. Our data suggest that the greater bioavailability of metals could be involved in JNK activation and, consequently, in the reduction of fiber coherence and increase in the viscoelasticity and cytotoxicity of BEAS cells. The adverse findings detected after exposure to crude DEP and to DEP/HEX reflect the toxic potential of diesel compounds. Considering the fact that the cells of the respiratory epithelium are the first line of defense between the body and the environment, our data contribute to a better understanding of the pathways leading to respiratory cell injury and provide evidence for the onset of or worsening of respiratory diseases caused by inorganic compounds present in DEP.
BMC Proceedings | 2013
Aline Custódio; Fabiane Cf Brito; Mara de Souza Junqueira; Roger Chammas; José E. Belizário
The Simian Virus 40 (SV40) large T antigen is multifunctional protein with DNA helicase, RNA helicase and ATPse activities which contribute to multistep tumorogenesis in rodents and humans. The Immortomouse mouse strain expresses a mutated large T antigen tsA58 oncogene under the control of the interferon inducible murine H-2Kb promoter on chromosome 16. Our aim was to establish a BALB/c strain of H-2Kb-tsA58 immortomice that could be utilized to investigate specific pathological and physiological patterns associated SV-40 oncogenicity and generation of conditionally immortal cells lines.
Drug Delivery | 2018
Angelica M. Patiño; Mara de Souza Junqueira; Xiaomeng Zhang; Kate M. Bailey; Arig Ibrahim-Hashim; Robert J. Gillies; Roger Chammas
Intravenous administration of hypertonic saline solution (HSS) induces systemic circulatory changes including increases in systemic blood pressure and effective circulating volume, as well as local effects on microvasculature. We analyzed the effects produced by 7.5% HSS administration on tumor hemodynamics through functional imaging studies. Blood velocity assessed by color Doppler ultrasound was increased after HSS injection compared to PBS in B16F10 (p=0.019), SK-MEL-147 (p=0.028), and 4T1 (p=0.015). No statistical differences were observed on the segmental kidney arteries (p=0.476). Dynamic contrast-enhanced ultrasound (CEUS) was used to assess functional blood volume in B16F10, HCT-116, and MDA-MB-231 tumor xenografts, kidney and muscle tissues (n=3 per group). After HSS injection, relative blood volume was increased in B16F10 (p=0.022) and HCT-116 (p=0.039) but not on MDA-MB-231 (p=0.186). There was a mild change that was not statistically significant on the normal tissues (kidney p=0.957; muscle p=0.104). Finally, dynamic contrast-enhanced MRI (DCE-MRI) was performed in B16F10 tumors (n=4) and showed that contrast distribution increases in the HSS group (p=0.002). All statistical tests were two sided. HSS 7.5% is a potential vehicle to transiently increase blood supply in specific tumors, and therefore could be used to enhance intratumoral delivery of different molecules for either tumor diagnosis or treatment. Supported by an UICC Yamagiwa-Yoshida grant and FAPESP (2013/06120-8 and 2015/22814-5). Citation Format: Angelica M. Patino, Mara S. Junqueira, Xiaomeng Zhang, Kate Bailey, Arig Ibrahim-Hashim, Robert J. Gillies, Roger Chammas. Transient increase of tumor perfusion using hypertonic saline [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A121.
American Journal of Pathology | 2007
Elizangela Silva-Monteiro; Luciana Reis Lorenzato; Oscar Kenji Nihei; Mara de Souza Junqueira; Gabriel A. Rabinovich; Daniel Kaiyuan Hsu; Fu Tong Liu; Wilson Savino; Roger Chammas; Déa Maria Serra Villa-Verde