SERGIO PAULO BYDLOWSKI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina - Líder
8 resultados
Resultados de Busca
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- Synergistic anti-tumor effects of the combination of a benzofuroxan derivate and sorafenib on NCI-H460 human large cell lung carcinoma cells(2014) TEIXEIRA, Sarah Fernandes; AZEVEDO, Ricardo Alexandre de; SALOMON, Maria Alejandra Clavijo; JORGE, Salomao Doria; LEVY, Debora; BYDLOWSKI, Sergio Paulo; RODRIGUES, Cecilia Pessoa; PIZZO, Celia Regina; BARBUTO, Jose Alexandre Marzagao; FERREIRA, Adilson KleberLung cancer is the most frequent and lethal human cancer in the world. Because is still an unsolved health issue, new compounds or therapeutic strategies are urgently needed. Furoxans are presented as potentials candidates for lung cancer treatment. Accordingly, we evaluated the efficacy of a benzofuroxan derivative, BFD-22, alone and combined with sorafenib against NCI-H460 cell line. We showed that BFD-22 has cytotoxic effects on the NCI-H460 cells. Importantly, the Combination Index (CI) evaluation revels that BFD-22 combined with sorafenib has a stronger cytotoxic effect. In addition, the combination induces apoptosis through extrinsic pathway, leading to TRAIL-R1/DR4-triggered apoptosis. Furthermore, BFD-22 combined with sorafenib increases ROS production and simultaneously reduces perlecan expression in the NCI-H460 cells. In accordance, tumor cells were arrested in the S-phase, and these anti-proliferative effects also inhibit cell migration. This is the first study reporting an advantage of BFD-22 combined with sorafenib as a new therapeutic strategy in the fight against lung cancer.
- Simvastatin induces osteogenic differentiation in human amniotic fluid mesenchymal stem cells (AFMSC)(2014) JANZ, Felipe de Lara; FAVERO, Giovani Marino; BOHATCH JR., Milton Sergio; DEBES, Adrianade Aguiar; BYDLOWSKI, Sergio PauloAmniotic fluid is a complex mixture composed of water, salts and different cells types derived from embryo exfoliation. Some of these cells present similar characteristics to mesenchymal stem cells as adherent properties, typical surface antigens and differentiation capacity. These cells are called amniotic fluid-derived mesenchymal stem cells (AFMSCs) and are easily obtained by amniocentesis, propagated in culture and differentiated in several cell types with specific inductions. In this study, we observe the ability of simvastatin, a 3-HMG-CoA reductase inhibitor, to induce AFSMCs osteogenic differentiation. When AFSMCs were incubated with medium containing simvastatin, it was observed morphological changes, calcium deposits formation confirmed by Alizarin Red stain. Differentiated cells also expressed typical osteogenic genes, as osteopontin and osteocalcin. In conclusion, simvastatin could be used as an optional osteogenic induction agent for amniotic fluid-derived mesenchymal stem cells.
- Short-term effects of 7-ketocholesterol on human adipose tissue mesenchymal stem cells in vitro(2014) LEVY, Debora; RUIZ, Jorge Luis Maria; CELESTINO, Andrea Turbuck; SILVA, Suelen Feitoza; FERREIRA, Adilson Kleber; ISAAC, Cesar; BYDLOWSKI, Sergio PauloOxysterols comprise a very heterogeneous group derived from cholesterol through enzymatic and nonenzymatic oxidation. Among them, 7-ketocholesterol (7-KC) is one of the most important. It has potent effects in cell death processes, including cytoxicity and apoptosis induction. Mesenchymal stem cells (MSCs) are multipotent cells characterized by self-renewal and cellular differentiation capabilities. Very little is known about the effects of oxysterols in MSCs. Here, we describe the short-term cytotoxic effect of 7-ketocholesterol on MSCs derived from human adipose tissue. MSCs were isolated from adipose tissue obtained from two young, healthy women. After 24 h incubation with 7-KC, mitochondrial hyperpolarization was observed, followed by a slight increase in the level of apoptosis and changes in actin organization. Finally, the IC50 of 7-KC was higher in these cells than has been observed or described in other normal or cancer cell lines.
- Human Paraoxonase-1 Activity Is Related to the Number of CD4+T-Cells and Is Restored by Antiretroviral Therapy in HIV-1-Infected Individuals(2014) MASELLI, Luciana Morganti Ferreira; CUNHA, Joel da; GUTIERREZ, Eliana Battaggia; MARANHAO, Raul Cavalcante; SPADA, Celso; BYDLOWSKI, Sergio PauloBackground. Paraoxonase-1 (PON1) activity is suggested to be altered in individuals infected with human immunodeficiency virus type-1 (HIV-1). We investigated PON1 activity in individuals receiving different regimens of highly active antiretroviral therapy (HAART). Methods. PON1 activity was evaluated in 91 HIV-1 seronegative and 624 HIV-1 infected individuals (115 were not undergoing therapy (ART-naive), and 509 were receiving HAART). HIV-1 infected individuals were treated with the following: efavirenz (EFV;n = 195) or nevirapine (NVP;n = 95) or lopinavir/ritonavir (LOP/r; n = 219). Serum levels of total cholesterol (TC), HDL, and low-density lipoprotein (LDL) fractions and the atherogenic indices (AI, TC : HDL, and LDL : HDL ratios) were determined. Results. PON1 activity (U/L) was lower in the ART-naive group compared with the other groups. PON1 activity correlated with CD4+ T-cell number of ART-naive group (r = 0, 121; P = 0, 014). The LOP/r group showed a reduction in HDL and an increase in AI (TC: HDL ratio) in comparison with other groups. Conclusion. PON1 activity was reduced in untreated individuals, but not in individuals receiving HAART. PON1 activity correlated with the number of CD4+ T-cells. The findings suggest that the activity of PON1 is associated with the immune status of HIV-1 infected individuals.
conferenceObject Was the PON1-55MM Polymorphism Associated to Higher Disease Severity in Common Variable Deficiency Patients?(2014) SINI, B. C.; BYDLOWSKI, S. P.; LEVY, Debora; MASELLI, Luciana M. F.; COHON, Andrea; KOKRON, Cristina M.; OLIVEIRA, Ana Karolina Barreto; KALIL, Jorge; BARROS, Myrthes Toledo- Association of Genetic Variants with Self-Assessed Color Categories in Brazilians(2014) DURSO, Danielle Fernandes; BYDLOWSKI, Sergio Paulo; HUTZ, Mara Helena; SUAREZ-KURTZ, Guilherme; MAGALHAES, Tiago R.; PENA, Sergio Danilo JunhoThe Brazilian population was formed by extensive admixture of three different ancestral roots: Amerindians, Europeans and Africans. Our previous work has shown that at an individual level, ancestry, as estimated using molecular markers, was a poor predictor of color in Brazilians. We now investigate if SNPs known to be associated with human skin pigmentation can be used to predict color in Brazilians. For that, we studied the association of fifteen SNPs, previously known to be linked with skin color, in 243 unrelated Brazilian individuals self-identified as White, Browns or Blacks from Rio de Janeiro and 212 unrelated Brazilian individuals self-identified as White or Blacks from Sao Paulo. The significance of association of SNP genotypes with self-assessed color was evaluated using partial regression analysis. After controlling for ancestry estimates as covariates, only four SNPs remained significantly associated with skin pigmentation: rs1426654 and rs2555364 within SLC24A5, rs16891982 at SLC45A2 and rs1042602 at TYR. These loci are known to be involved in melanin synthesis or transport of melanosomes. We found that neither genotypes of these SNPs, nor their combination with biogeographical ancestry in principal component analysis, could predict self-assessed color in Brazilians at an individual level. However, significant correlations did emerge at group level, demonstrating that even though elements other than skin, eye and hair pigmentation do influence self-assessed color in Brazilians, the sociological act of self-classification is still substantially dependent of genotype at these four SNPs.
- Detection of Plasmodium falciparum and Plasmodium vivax subclinical infection in non-endemic region: implications for blood transfusion and malaria epidemiology(2014) MASELLI, Luciana M. F.; LEVY, Debora; LAPORTA, Gabriel Z.; MONTEIRO, Aline M.; FUKUYA, Linah A.; FERREIRA-DA-CRUZ, Maria F.; DANIEL-RIBEIRO, Claudio T.; DORLHIAC-LLACER, Pedro E.; SALLUM, Maria Anice M.; BYDLOWSKI, Sergio P.Background: In Brazil, malaria is endemic in the Amazon River basin and non-endemic in the extra-Amazon region, which includes areas of Sao Paulo state. In this state, a number of autochthonous cases of malaria occur annually, and the prevalence of subclinical infection is unknown. Asymptomatic infections may remain undetected, maintaining transmission of the pathogen, including by blood transfusion. In these report it has been described subclinical Plasmodium infection in blood donors from a blood transfusion centre in Sao Paulo, Brazil. Methods: In this cross-sectional study, representative samples of blood were obtained from 1,108 healthy blood donors at the Fundacao Pro-Sangue Hemocentro de Sao Paulo, the main blood transfusion centre in Sao Paulo. Malaria exposure was defined by the home region (exposed: forest region; non-exposed: non-forest region). Real-time PCR was used to detect Plasmodium falciparum and Plasmodium vivax. Subclinical malaria cases were geo-referenced. Results: Eighty-four (7.41%) blood donors tested positive for Plasmodium; 57 of these were infected by P. falciparum, 25 by P. vivax, and 2 by both. The prevalence of P. falciparum and P. vivax was 5.14 and 2.26, respectively. The overall prevalence ratio (PR) was 3.23 (95% confidence interval (CI) 2.03, 5.13); P. falciparum PR was 16.11 (95% CI 5.87, 44.21) and P. vivax PR was 0.47 (95% CI 0.2, 1.12). Plasmodium falciparum subclinical malaria infection in the Atlantic Forest domain was present in the mountain regions while P. vivax infection was observed in cities from forest-surrounded areas. Conclusions: The presence of Plasmodium in healthy blood donors from a region known as non-endemic, which is important in the context of transfusion biosafety, was described. Infected recipients may become asymptomatic carriers and a reservoir for parasites, maintaining their transmission. Furthermore, P. falciparum PR was positively associated with the forest environment, and P. vivax was associated with forest fragmentation.
- Finding connections in the unexpected detection of Plasmodium vivax and Plasmodium falciparum DNA in asymptomatic blood donors: a fact in the Atlantic Forest(2014) SALLUM, Maria Anice Mureb; DANIEL-RIBEIRO, Claudio Tadeu; LAPORTA, Gabriel Zorello; FERREIRA-DA-CRUZ, Maria de Fatima; MASELLI, Luciana Morganti Ferreira; LEVY, Debora; BYDLOWSKI, Sergio PauloA recent paper in Malaria Journal reported the observation of unexpected prevalence rates of healthy individuals carrying Plasmodium falciparum (5.14%) or Plasmodium vivax (2.26%) DNA among blood donors from the main transfusion centre in the metropolitan Sao Paulo, a non-endemic area for malaria. The article has been challenged by a group of authors who argued that the percentages reported were higher than those found in blood banks of the endemic Amazon Region and also that that paper had not considered the literature on the classical dynamics of malaria transmission in the Atlantic Forest, which involves Anopheles (Kerteszia) cruzii and bromeliad malaria, due to P. vivax and Plasmodium malariae parasites, but not P. falciparum. The present commentary paper responds to this challenge and brings evidence and literature data supporting that the observed prevalence ratios may indicate a proportion of individuals that are exposed to Plasmodium transmission in permissive environments; that blood carrying parasite DNA may not be necessarily infective if used in transfusion; and that in the literature, there are examples supporting the circulation of P. falciparum in the area.