Papers by Sergio Bydlowski
Blood, Nov 20, 2009
Abstract 1939 Poster Board I-962 Background: Diffuse large B-cell lymphoma (DLBCL) is the most co... more Abstract 1939 Poster Board I-962 Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoma. It is a heterogeneous disease. Approximately 40% of the patients respond well to chemotherapy based on rituximab-CHOP (R-CHOP). The prognosis for the other 60% is poor and only half of the patients survives 5 years after the onset of the disease. Glutathione-S-transferase (GST) genes, including GSTM1 (GST mu 1), GSTT1 (GST Tetha 1), and GSTP1 (GST pi 1), are a complex multigene family involved in metabolism and detoxification of chemical agents such as alkylators and steroids. They are involved with cell proliferation and cell survival. Since many of these drugs are regularly used to treat LDGCB we studied the GST gene polymorphisms regarding there involvement in prognosis and clinical features of this disease. Methods: 79 patients with DLBCL classified according to WHO criteria were studied for GSTM1 or GSTT1 null deletion polymorphism by multiplex PCR and GSTP1…
Acta Tropica, Mar 1, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Photodiagnosis and Photodynamic Therapy, Dec 1, 2020
Uptake of silver, gold, and hybrids silver-iron, gold-iron and silver-gold aminolevulinic acid na... more Uptake of silver, gold, and hybrids silver-iron, gold-iron and silver-gold aminolevulinic acid nanoparticles by MCF-7 breast cancer cells, Photodiagnosis and Photodynamic Therapy (2020), doi:
Blood, Nov 19, 2010
Abstract 5078 Background: Low-affinity receptor for the Fcγ region of immunoglobulin G (IgG) (Fcγ... more Abstract 5078 Background: Low-affinity receptor for the Fcγ region of immunoglobulin G (IgG) (FcγR) is constitutively expressed on resting human neutrophils. These receptor, termed FcγRIIa display biallelic polymorphism which have functional consequences with respect to binding and/or ingestion of targets opsonized by human IgG subclass antibodies. Rituximab is a chimeric monoclonal antibody directed against CD20, an antigen found in most B-cell malignancies. Multiple mechanisms have been proposed for the activity of Rituximab, including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and a direct proapoptotic effect. F(ab′)2 Rituximab homodimers were shown to be effective in inducing apoptosis of B-cell lymphoma cell lines in vitro. Recently, it have been established that ADCC is important as predominant mechanism of lymphoma cell clearance and that Fcγ receptors (FcγRs) are critical for the in vivo actions of Rituximab in non-Hodgkin lymphoma (NHL). A genomic polymorphism at amino acid 131 of FcγRIIA has been described whereby the presence of Histidine (H) rather than Arginine is associated with responses to the CD20-directed immunoglobulin G1 (IgG1) Rituximab among patients with indolent lymphoma. FcγRIIA genotype have been associated with a better clinical and molecular response in follicular lymphoma patients treated as first line therapy with Rituximab alone and in patients with diffuse large B-cell lymphoma (DLBCL) treated with the concomitant administration of Rituximab and CHOP (R-CHOP). Methods: Here we analyzed the role of specific polymorphism of activating FcγRIIA in 64 patients with DLBCL treated with R-CHOP concerning prediction complete response (CR), Progression Free Survival (PFS) and Overall Survival (OS) using a polymerase chain reaction-restriction fragment length polymorphism method. Results: The median age of the patients was 48.6 years. Out of the 64 patients (32%), were stage III-IV and 27 (42.5%) had more than 2 factors of the International Prognostic Index. Fity-six (89%) had CR and 7 (9.5%) had refractory disease (RD). Seven (11%) of the patients presented relapses. Deaths occurred in 6 (9.3%) patients with follow up of 19,5 months (range 21,3-50,1). The distribution of FcγRIIA polymorphism genotypes was: 15 (23,4%) HH, 30(46,9%) HR and 19(29,7%) RR, while considering only two groups (HH and R allele (HR and RR) was 15 (23,4%) and 49 (76,6%). There were no statistically significant differences in the genotypes groups according prognostic factors. In addition, there were not differences between response rate and FcγRIIA genotypes polymorphism: the CR in HH and HR/ RR were respectively 80% and 89%, p=0,377. It was not found differences regarding FcγRIIa. HH genotype presented a median PFS and OS. Thus, PFS HH genotype presented a median PFS 20,96 ± 10,49 months versus HR/RR median PFS 12,03 ± 7,71 months, p = 0,765, and OS 23,26 ± 10,42 months versus HR/ RR median OS 12,7 ± 7,42 months, p =0,98. Conclusions: Contrary to recent report we showed that FcγRIIA polymorphism is not associated to overall response, PFS and OS in patients with DLBCL treated with R-CHOP. Disclosures: No relevant conflicts of interest to declare.
INVESTIGAÇÃO, Oct 17, 2016
A estrongiloidiase e uma infeccao potencialmente grave em pacientes imunodeprimidos. O diagnostic... more A estrongiloidiase e uma infeccao potencialmente grave em pacientes imunodeprimidos. O diagnostico parasitologico pelas tecnicas tradicionais tem baixa sensibilidade. Dessa forma, a disponibilizacao de tecnicas diagnosticas sensiveis e especificas e desejavel, sobretudo no contexto das imunodepressoes, pois a identificacao e o tratamento da helmintiase sao fundamentais. As tecnicas sorologicas buscam melhores parâmetros de diagnosticos, entretanto os resultados sao muito variados. O objetivo deste trabalho e aprimorar o imunodiagnostico da estrongiloidiase humana identificando proteinas imunodominantes, utilizando a tecnica de Western-blotting (WB). Foram utilizadas as fracoes soluvel (TSL) e de membrana (TML) do estagio evolutivo de larvas filarioides Strongyloides venezuelensis . Foram utilizadas amostras de soros de individuos positivos para S. stercoralis , para outras parasitoses e negativos. Para identificacao das bandas imunogenicas foi realizado o WB e as proteinas reveladas foram recortadas de geis replicas para digestao em peptidios tripticos e posterior analise por espectrometria de massas. Diferentes componentes antigenicos foram reconhecidos por anticorpos IgG de pacientes com estrongloidiase, sendo as bandas de 30-40kDa como as mais frequentes. Apos analise por espectrometria de massas, as proteinas imunoreativas identificadas correspondiam a enzimas e proteinas de citoesqueleto, destacando galectinas e actina como as proteinas de maior abundância.
InTech eBooks, Feb 7, 2018
Anemia presents a global public health problem. It is related to several factors, ranging from de... more Anemia presents a global public health problem. It is related to several factors, ranging from deficiency in nutrients from food to genetic alterations in iron absorption and metabolism. In this context, hepcidin is a peptide molecule that regulates iron homeostasis. Hepcidin is synthesized, in part, by hepatocytes. In physiological conditions, increased serum transferrin, serum iron, inflammation, and erythropoiesis trigger stimuli that promote hepcidin antimicrobial peptide (HAMP) gene transcription and hepcidin synthesis. However, in pathological situations, an overexpression of hepcidin occurs, an increase in the plasma concentration that damages the organism. Hepcidin contributes to the pathogenesis of iron deficiency anemia, anemia of inflammation, in hemoglobinopathies. Then, there is a restriction of the availability of iron to the tissues and the formation of new erythroid precursors, with the consequent development of anemia.
Vitamins and hormones, 2021
Highlights-Oxysterols plays several roles in pathophysiological processes-Mesenchymal stem cells ... more Highlights-Oxysterols plays several roles in pathophysiological processes-Mesenchymal stem cells (MSCs) have properties of differentiation into other cell types-The effects of oxysterols on MSCs differentiation into osteoblasts and adipocytes are reviewed-The main pathways involved in these effects are evaluated
American Journal of Physiology-heart and Circulatory Physiology, 1987
A systematic study of the ontogeny of aortic 6-ketoprostaglandin F1 alpha synthesis from birth to... more A systematic study of the ontogeny of aortic 6-ketoprostaglandin F1 alpha synthesis from birth to adult life and the effect of premature weaning on this process was investigated in rabbits. Prostacyclin (PGI2) synthesis by both endogenous and exogenous arachidonic acid and its relation to aortic arachidonic acid content was determined. It was found that 1) PGI2 synthesis from endogenous arachidonic acid increased with age, whereas 2) PGI2 synthesis from exogenous arachidonic acid decreased. This correlated with a decrease in the incorporation of [14C]arachidonic acid into phospholipids with age. Aortic arachidonic acid concentration did not change from birth until 3 wk of life but increased markedly by 5 wk of age. Premature weaning caused a decrease in the synthesis of aortic PGI2 and in aortic arachidonic acid concentration initially, but the changes did not persist in later life. These studies suggest that the utilization of exogenous arachidonic acid by aorta decreases after birth perhaps due to maturity of the enzyme systems that synthesize and utilize endogenous substrates.
Boletim da Academia Nacional de Medicina, 2022
Journal of Veterinary Internal Medicine, 2007
Biomedical science and engineering, Jun 2, 2015
Mesenchymal stem cells (MSCs) are described as undifferentiated cells with high capacity for self... more Mesenchymal stem cells (MSCs) are described as undifferentiated cells with high capacity for selfrenewal and differentiation ability in different tissues. MSCs are found in various locations in the adult organism as bone marrow, adipose tissue; and in fetal tissues as umbilical cord, placenta and amniotic fluid. They are able to produce and secrete a number of bioactive molecules with different effects: anti-fibrotic, angiogenic and mitogen. These cells also present a great immunomodulatory and anti-inflammatory potential described in experimental and human models. Several studies have demonstrated the ability of MSCs to suppress the proliferation and activation of T, B and NK cells in vitro and in vivo. Its low immunogenic action causes are not recognized by HLA mismatched receptor complex because they express low levels of MHC-I do not express MHC-II and costimulatory molecules CD40, CD80 and CD86. Because of these unique characteristics, MSCs arouse great interest in possible clinical applications in the therapy of diseases that affect the immune system. Although depending on the tissue microenvironment, the MSCs can also trigger inflammatory events. In this work, we described the main factors and another structures involved in MSCs immunoregulation.
Frontiers in Immunology, Nov 12, 2021
metabolism and mitochondrial dysfunction in CCC myocardium which may be in part linked to IFN-gam... more metabolism and mitochondrial dysfunction in CCC myocardium which may be in part linked to IFN-gamma. This may partially explain the worse prognosis of CCC as compared to DCM or IC.
Blood, Nov 20, 2009
Abstract 4994 Background Low-affinity receptor for the Fc region of immunoglobulin G (IgG) (FcγR)... more Abstract 4994 Background Low-affinity receptor for the Fc region of immunoglobulin G (IgG) (FcγR) is constitutively expressed on resting human neutrophils. These receptor, termed FcγRIIa display biallelic polymorphism which have functional consequences with respect to binding and/or ingestion of targets opsonized by human IgG subclass antibodies. Rituximab is a chimeric monoclonal antibody directed against CD20, an antigen found in most B-cell malignancies. Multiple mechanisms have been proposed for the activity of Rituximab, including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and a direct proapoptotic effect. F(ab')2 Rituximab homodimers were shown to be effective in inducing apoptosis of B-cell lymphoma cell lines in vitro. Recently, it have been established that ADCC is important as predominant mechanism of lymphoma cell clearance and that Fcγ receptors (FcγRs) are critical for the in vivo actions of Rituximab in non-Hodgkin lymphoma (NHL). A genomic polymorphism at amino acid 131 of FcγRIIA has been described whereby the presence of Histidine (H) rather than Arginine is associated with responses to the CD20-directed immunoglobulin G1 (IgG1) Rituximab among patients with indolent lymphoma. FcγRIIA genotype have been associated with a better clinical and molecular response in follicular lymphoma patients treated as first line therapy with Rituximab alone and in patients with diffuse large B-cell lymphoma (DLBCL) treated with the concomitant administration of Rituximab and CHOP (R-CHOP). Methods Here we analyzed the role of specific polymorphism of activating FcγRIIA in 42 patients with DLBCL treated with R-CHOP concerning prediction complete response (CR) using a polymerase chain reaction-restriction fragment length polymorphism method. Results The median age of the patients was 48 years (15 to 82). Out of the 42 patients 18 (42.8%) were stage III-IV and 17 (40.4%) had more than 2 factors of the International Prognostic Index. Thirty-seven (87.6%) had CR, 1 (2.3%) had partial remission (PR) and 4 (10.1%) had refractory disease (RD). Four ( 10.8%) of the patients that acquired CR relapsed. Deaths occurred in 3 (7.1%) patients with follow up of 2 years. Eight (19%) patients showed polymorphism HH, 21 (50%) HR and 13 (31%) RR. The univariate analysis did not show correlation between FcγRIIa H/H or R allele polymorphism and CR (p > 0.05). Conclusion Contrary to recent report we showed that FcγRIIa polymorphism is not associated to overall response in patients with DLBCL treated with Rituximab. Disclosures No relevant conflicts of interest to declare.
Acta Haematologica, 2017
Iron is an essential metal for cell survival that is regulated by the peptide hormone hepcidin. H... more Iron is an essential metal for cell survival that is regulated by the peptide hormone hepcidin. However, its influence on certain diseases is directly related to iron metabolism or secondary to underlying diseases. Genetic alterations influence the serum hepcidin concentration, which can lead to an iron overload in tissues, as observed in haemochromatosis, in which serum hepcidin or defective hepcidin synthesis is observed. Another genetic imbalance of iron is iron-refractory anaemia, in which serum concentrations of hepcidin are increased, precluding the flow and efflux of extra- and intracellular iron. During the pathogenesis of certain diseases, the resulting oxidative stress, as well as the increase in inflammatory cytokines, influences the transcription of the HAMP gene to generate a secondary anaemia due to the increase in the serum concentration of hepcidin. To date, there is no available drug to inhibit or enhance hepcidin transcription, mostly due to the cytotoxicity described in the in vitro models. The proposed therapeutic targets are still in the early stages of clinical trials. Some candidates are promising, such as heparin derivatives and minihepcidins. This review describes the main pathways of systemic and genetic regulation of hepcidin, as well as its influence on the disorders related to iron metabolism.
Brain and behavior, Feb 16, 2021
This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
British Journal of Cancer, Nov 1, 1995
S _ry We searched for mutations of the p53 gene in 25 phaeochromocytomas using polymerase chain r... more S _ry We searched for mutations of the p53 gene in 25 phaeochromocytomas using polymerase chain reaction-e strand conformation polymorphism (PCR-SSCP) analysis of the entire conserved regon of the gene, cxons 4-8; expression of the p53 protein was assessed by immunohistochemistry. No mutations were found, while a polymorphism in codon 72 was observed. Immunohistochemistry revealed nudear p53 ovexession in one tumour sample. We conchlde that mutations of the 'hotspot' regon of the p53 gene do not seem to play a role in the pathogenesis of phaeochromocytoma. Keyword phaeochromocytoma; p53 gene; mutation; immunohistochemistry; mokcular screening; polymorphism Although recent studies have identfied the gene involved in familial forms of phaeochromocytoma (Viskochil et al., 1990;
Molecules, Jul 9, 2007
The antioxidant activity of flavonoids is believed to increase when they are coordinated with tra... more The antioxidant activity of flavonoids is believed to increase when they are coordinated with transition metal ions. However, the literature on this subject is contradictory and the outcome seems to largely depend on the experimental conditions. In order to understand the contribution of the metal coordination and the type of interaction between a flavonoid and the metal ion, in this study a new metal complex of Cu (II) with naringin was synthesized and characterized by FT-IR, UV-VIS, mass spectrometry (ESI-MS/MS), elemental analysis and 1 H-NMR. The results of these analyses indicate that the complex has a Cu (II) ion coordinated via positions 4 and 5 of the flavonoid. The antioxidant, anti-inflammatory and antimicrobial activities of this complex were studied and compared with the activity of free naringin. The Naringin-Cu (II) complex 1 showed higher antioxidant, anti-inflammatory and tumor cell cytoxicity activities than free naringin without reducing cell viability.
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Papers by Sergio Bydlowski