Browsing by Author "Borges, Karina Braga Gomes"

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    Efeitos toxicogenéticos do resveratrol em células de câncer de bexiga com diferentes status do gene TP53.
    (2020) Almeida, Tamires Cunha; Silva, Glenda Nicioli da; Silva, Glenda Nicioli da; Borges, Karina Braga Gomes; Machado, Carlos Renato; Isoldi, Mauro César; Souza, Gustavo Henrique Bianco de
    A atividade antitumoral do resveratrol, composto polifenólico encontrado principalmente nas uvas, tem sido estudada em diversos tipos de câncer. No câncer de bexiga, seus efeitos antiproliferativos já foram demostrados, tanto in vitro quanto in vivo, entretanto pouco se sabe sobre seu mecanismo de ação. Nesse contexto, o presente estudo teve como objetivo avaliar o potencial antineoplásico e os possíveis mecanismos de ação molecular do resveratrol em células tumorais de bexiga com diferentes status do gene TP53 (RT4 - TP53 selvagem; 5637 e T24 - TP53 mutado). Avaliou-se os efeitos do resveratrol em relação a citotoxicidade, alterações morfológicas, sobrevivência clonogênica, genotoxicidade, mutagenicidade, produção de espécies reativas de oxigênio, progressão do ciclo celular, taxas de apoptose/necrose, migração celular, metilação global, imunocitoquímica para p53 e PCNA e expressão dos genes AKT, CDH1, CTNNBIP1, DNMT1, FGFR3, HAT, HDAC1, HOXB3, mTOR, MYC, PLK1, RASSF1A, SMAD4 e SRC. Os resultados mostraram que o resveratrol possui efeito citotóxico em todas as linhagens estudadas, sendo a linhagem TP53 selvagem mais sensível à ação desse composto. Em relação aos efeitos a longo prazo, observou-se que o resveratrol causou redução do número de colônias em todas as linhagens, juntamente com redução da expressão do gene PLK1. Aumento significativo de danos primários ao DNA foi detectado em todas as linhagens e provavelmente ocorreu devido aos efeitos pró-oxidantes do resveratrol. Aumento significativo das taxas de apoptose foram encontradas na linhagem TP53 selvagem ao mesmo tempo em que ocorreu redução da expressão dos genes AKT, mTOR e SRC. A redução da migração celular foi acompanhada pela redução da expressão do gene SMAD4 e aumento da expressão de CDH1. Além disso, os efeitos antiproliferativos do composto na linhagem TP53 selvagem foram acompanhados de modulação dos genes HAT, HOXB3 e DNMT1. Nas linhagens mutadas para o gene TP53 pode-se observar que o resveratol leva a parada do ciclo celular na fase S, juntamente com redução da expressão do gene PLK1. Também foi observada inibição da migração celular acompanhada do aumento da expressão dos genes CDH1 e CTNNBIP1. Adicionalmente, houve modulação de vias relacionadas a HOXB3, RASSF1A e HAT na linhagem T24. Concluindo, o resveratrol possui atividade antiproliferativa independente do status de TP53 em células tumorais de bexiga, entretanto, os efeitos antineoplásicos observados devem-se a diferentes mecanismos de ação.
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    A new index to discriminate between iron deficiency anemia and thalassemia trait.
    (2016) Matos, Januária Fonseca; Dusse, Luci Maria Sant Ana; Borges, Karina Braga Gomes; Castro, Ricardo L. V. de; Vital, Wendel Coura; Carvalho, Maria das Graças
    Background: The most common microcytic and hypochromic anemias are iron deficiencyanemia and thalassemia trait. Several indices to discriminate iron deficiency anemia fromthalassemia trait have been proposed as simple diagnostic tools. However, some of the bestdiscriminative indices use parameters in the formulas that are only measured in moderncounters and are not always available in small laboratories.The development of an index with good diagnostic accuracy based only on parametersderived from the blood cell count obtained using simple counters would be useful in theclinical routine. Thus, the aim of this study was to develop and validate a discriminativeindex to differentiate iron deficiency anemia from thalassemia trait. Methods: To develop and to validate the new formula, blood count data from 106 (thalassemiatrait: 23 and iron deficiency: 83) and 185 patients (thalassemia trait: 30 and iron deficiency:155) were used, respectively. Iron deficiency, _-thalassemia trait and _-thalassemia trait wereconfirmed by gold standard tests (low serum ferritin for iron deficiency anemia, HbA2> 3.5%for _-thalassemia trait and using molecular biology for the _-thalassemia trait).Results: The sensitivity, specificity, efficiency, Youden’s Index, area under receiver operatingcharacteristic curve and Kappa coefficient of the new formula, called the Matos & CarvalhoIndex were 99.3%, 76.7%, 95.7%, 76.0, 0.95 and 0.83, respectively. Conclusion: The performance of this index was excellent with the advantage of being solelydependent on the mean corpuscular hemoglobin concentration and red blood cell countobtained from simple automatic counters and thus may be of great value in underdevelopedand developing countries.
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    Response to the assessment of the Matos & Carvalho index by Hoffmann and Urrechaga.
    (2017) Matos, Januária Fonseca; Dusse, Luci Maria Sant'Ana; Borges, Karina Braga Gomes; Vital, Wendel Coura; Carvalho, Maria das Graças
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    The polymorphism rs17782313 near MC4R gene is related with anthropometric changes in women submitted to bariatric surgery over 60 months.
    (2017) Resende, Cristina Maria Mendes; Durso, Danielle Fernandes; Borges, Karina Braga Gomes; Pereira, Rafaela Messias; Rodrigues, Gisele Kuhlmann Duarte; Rodrigues, Kathryna Fontana; Silva, José Luiz Padilha da; Rodrigues, Erica Castilho; Franco, Glória Regina; Leite, Jacqueline Isaura Alvarez
    Objective: Evaluate whether the polymorphism rs17782313 near MC4R gene influences long-term outcomes after bariatric surgery. Methods: The rs16782313 polymorphism was genotyped in 217 individuals undergoing bariatric surgery and analyzed in detail in 141 women. Data for comorbidities, BMI, excess weight loss (EWL), and body composition were obtained before and during 60 months after surgery. Results: The risk allele was found in 65 (47%) of the 141 women. Pre-surgical body weight and BMI were higher in carriers of the rs17782313 polymorphism (CC þ CT group) than in non-carriers (TT group) (p ¼ 0.039 and 0.047, respectively). The number of women who acquired surgical success (EWL > 50%), was lower in CC þ CT group compared to TT group (p ¼ 0.015). The minimum BMI seen during the 60 months of follow-up was higher in CC þ CT group compared to TT group (p ¼ 0.028). The number of women who presented BMI < 30 kg/m2 (no longer classified as obesity) after 24 months of surgery was inferior in CC þ CT group (6 out 35 patients e 17%) than in TT group (19 out 49 patients e 37%, p ¼ 0.043). Moreover, the number of patients maintaining BMI > 35 kg/m2 were higher carriers (18 out 35 patients e 51%) compare to non-carriers (16 out 49 patients e 32%, p ¼ 0.045). Conclusion: Women with extreme obesity carrying rs17782313 MC4R polymorphism present a higher pre-surgical BMI, are more unlikely to reach non-obesity BMI (<30 kg/m2) and tend to maintain a BMI > 35 kg/m2 that characterize treatment failure.
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    Toxicological study of a new doxorubicin-loaded pH-sensitive liposome : a preclinical approach.
    (2018) Silva, Juliana de Oliveira; Miranda, Sued Eustaquio Mendes; Leite, Elaine Amaral; Sabino, Adriano de Paula; Borges, Karina Braga Gomes; Cardoso, Valbert Nascimento; Cassali, Geovanni Dantas; Guimarães, Andrea Grabe; Oliveira, Mônica Cristina de; Barros, André Luís Branco de
    Doxorubicin (DOX) is widely used in cancer treatment, however, the use of this drug is often limited due to its cardiotoxic side effects. In order to avoid these adverse effects, the encapsulation of DOX into nanosystems has been used in the last decades. In this context, pH-sensitive liposomes have been shown promising for delivering cytotoxic agents into tumor cells, however, the lack of information about in vivo toxicity of this nanocarrier has impaired translational studies. Therefore, the aim of this work was to investigate the acute toxicity and cardiotoxicity of DOX-loading pH-sensitive liposomes (SpHL-DOX). To achieve this, female BALB/c mice, after intravenous administration, were monitored by means of clinical, laboratory, histopathological and electrocardiographic (ECG) analyses. Results indicate that SpHL was able to prevent renal toxicity and the hepatic injury was less extensive than free DOX. In addition, lower body weight loss was associated with less ECG QT interval prolongation to animals receiving SpHL-DOX (14.6 ± 5.2%) compared to animals receiving free DOX (35.7 ± 4.0%) or non-pH-sensitive liposomes (nSpHL-DOX) (47.0 ± 9.8%). These results corroborate with SpHL-DOX biodistribution studies published by our group. In conclusion, the SpHL-DOX showed less toxic effects on mice compared to free DOX or nSpHL-DOX indicating that SpHL-DOX is a promising strategy to reduce the serious cardiotoxic effects of DOX.