Navegando por Autor "Sabino, Adriano de Paula"

Agora exibindo 1 - 8 de 8

Are the polymorphisms in ACE and ESR1 genes associated with preeclampsia occurrence?
(2019) Lopes, Ana Cristina dos Santos; Perucci, Luiza Oliveira; Evangelista, Fernanda Cristina Gontijo; Godoi, Lara Carvalho; Sabino, Adriano de Paula; Silva, André Talvani Pedrosa da; Dusse, Luci Maria Sant'Ana; Alpoim, Patrícia Nessralla
Association among ACE, ESR1 polymorphisms and preeclampsia in Brazilian pregnant women.
(2019) Lopes, Ana Cristina dos Santos; Perucci, Luiza Oliveira; Evangelista, Fernanda Cristina Gontijo; Godoi, Lara Carvalho; Sabino, Adriano de Paula; Gomes, Karina Braga; Silva, André Talvani Pedrosa da; Dusse, Luci Maria Sant'Ana; Alpoim, Patrícia Nessralla
Background: Genetic, immune and environmental factors are involved in preeclampsia (PE) etiopathogenesis. Considering that hypertension and poor placental perfusion are important features in PE, polymorphisms in the angiotensin-converting enzyme (ACE) and estrogen nuclear receptor 1 (ESR1) genes could be involved in the predisposition and/or development of the disease. The aim of this study was to evaluate if polymorphisms in ACE and ESR1 genes were associated with PE occurrence. Material and Methods: This case-control study included 209 Brazilian pregnant women (107 with severe PE and 102 normotensive controls). The polymorphisms were investigated by polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis. Results: No significant difference between PE versus normotensive pregnant women, as well as early versus late PE, was observed when compared the allelic and genotypic frequencies of insertion/deletion polymorphism in intron 16 of the ACE gene and the single nucleotide polymorphisms (SNPs - rs2234693 and rs9340799) of the ESR1 gene. Conclusion: This pioneer study involving Brazilian women showed no association among the studied polymorphisms and PE, which suggests that ins/del ACE and SNPs ESR1 do not contribute to this disease occurrence in Brazil.
Efeitos citotóxicos e toxicogenômicos da silibinina em células de câncer de bexiga com diferentes status do gene TP53.
(2019) Barros, Tatiane Martins Barcelos; Silva, Glenda Nicioli da; Silva, Glenda Nicioli da; Sabino, Adriano de Paula; Souza, Gustavo Henrique Bianco de
A silibinina, um composto natural extraído de frutos e sementes de Silybum marianum, demonstrou propriedades antitumorais em células de câncer de bexiga; no entanto, o papel do gene TP53 nestes efeitos não é claro. Para entender melhor os mecanismos moleculares e antiproliferativos deste composto, células de câncer de bexiga com diferentes status do gene TP53, RT4 (tumor de baixo grau, gene TP53 selvagem), 5637 (grau 2, tumor de alto grau, gene TP53 mutado) e T24 (grau 3, tumor de alto grau, gene TP53 mutado), foram tratadas com silibinina nas concentrações 1; 5; 10; 50; 100 e 150 μM. Vários parâmetros foram avaliados, incluindo citotoxicidade, efeito pró-oxidante, alterações morfológicas, migração celular, progressão do ciclo celular, perfil de metilação global e expressão relativa dos genes HOXB3, c-MYC, PLK1, SMAD4, SRC, HAT, HDAC e RASSF1A. Os resultados mostraram que a silibinina apresentou efeitos citotóxicos e próoxidantes nas três linhagens celulares. A interferência significativa na migração celular e a parada do ciclo celular na fase G2 / M foram observadas em células com o gene TP53 mutado. Além disso, a silibinina induziu hipometilação global de DNA nas células com maior grau de tumor. Para as células TP53 do tipo selvagem, o conteúdo sub-G1 estava presente de forma significativa. Além disso, houve modulação da expressão gênica dos oncogenes responsáveis pelo crescimento celular (SMAD e c-MYC), migração (SRC e HOXB3), cinética do ciclo celular (PLK1), angiogênese (HOXB3) e genes associados a eventos epigenéticos como acetilação de DNA (HAT) e desacetilação (HDAC). Em conclusão, a silibinina inibe a proliferação celular independentemente do status de TP53. Entretanto, os efeitos sobre o ciclo celular, a migração celular e a expressão gênica são dependentes do status de TP53.
Expressão de pRB, ki-67 e da oncoproteína E7 do papilomavírus humano nas lesões intraepiteliais cervicais e no carcinoma epidermoide invasor.
(2019) Assis, Bárbara Letícia Gonçalves de; Lima, Angélica Alves; Sabino, Adriano de Paula; Vieira, Paula Melo de Abreu; Lima, Angélica Alves
O câncer cervical é uma das doenças mais frequentes que acometem a população feminina. O Papilomavírus Humano de alto risco oncogênico (HR-HPV), principal fator de risco do câncer cervical, interfere no ciclo celular do hospedeiro levando à desregulacão e progressão para lesões neoplásicas. Esta interferência pode levar a indicação de marcadores úteis no prognóstico e no diagnóstico da doença. A maioria dos marcadores que vêm sendo investigados são proteínas virais, de ciclo celular e de proliferação. Assim, neste estudo foi avaliada a expressão imunoistoquímica das proteínas pRb, Ki-67 e E7-HPV nas lesões intraepiteliais cervicais e no carcinoma epidermoide invasor, correlacionando-as com a infecção por HR-HPV e a expressão imunoistoquímica de p16, p53, PCNA e L1/HPV. O trabalho foi realizado com 150 amostras de biópsias cervicais, distribuídas em Cervicite (C), Neoplasia Intraepitelial Cervical (NIC) de graus 1, 2 e 3 e Carcinoma Epidermoide Invasor (CEI). A expressão das proteínas foi avaliada pela técnica de imunoistoquímica utilizando anticorpos monoclonais anti-pRb, anti-ki-67 e anti-E7-HPV16. A pesquisa de HR-HPV foi feita por PCR tempo real que possibilitou a detecção de 14 tipos virais de alto risco oncogênico (HR-HPV). Análise inicial mostrou que as proteínas de ciclo celular, de proliferação e do HPV apresentaram associação com o grau da lesão (p<0,05), sendo pRb, p53 e L1/HPV menos expressas nas lesões mais graves (NIC3/CEI) enquanto ki-6716, PCNA e p16 foram mais expressas nessas lesões. Em relação à infecção viral, HR-HPV foi detectado em 61,3% das amostras, com predomínio de HPV 16 em NIC3/CEI e de outros tipos virais de alto risco em NIC1/NIC2. HPV 18 foi detectado apenas em amostras NIC3/CEI. A presença de HR-HPV foi associada ao diagnóstico histopatológico. Foi observada alta positividade de HPV em todas as amostras e maior frequência de HR-HPV nas lesões mais graves. Os resultados mostraram menor expressão de E7/HPV em NIC2 e CEI. Nas lesões cervicais, independente do grau, houve predomínio de E7+/HRHPV+ (NIC1 = 50,0%; NIC2 = 36,7% e NIC3 = 60,0%), exceto em CEI onde o padrão E7-/HRHPV+ foi o mais presente (43,3%). Em cervicite os padrões mais encontrados foram E7-/HRHPV- (30,8%) e E7+/HRHPV- (57,7%). Na análise de associação das proteínas de ciclo celular com o diagnóstico histopatológico foi observada significativa diminuição da expressão de pRb e aumento de p16 nas lesões mais graves nas amostras positivas para HR-HPV e E7/HPV. A avaliação do desempenho diagnóstico apontou que a associação do teste de pRb com p16 (A: NIC1+ = 87,0%) ou com HR-HPV (A: NIC1+ = 80,8%) tiveram as melhores acurácias para diferenciar lesões NIC1+. A associação do teste de pRb com o de L1/HPV (A: NIC2+ = 80,1%) apresentou desempenho satisfatório na avaliação de NIC2+. Os resultados sugerem que a análise de pRb, p16 e HR-HPV, isolados ou associados, podem ser úteis como possíveis marcadores auxiliando na diferenciação dos graus das lesões intraepiteliais cervicais.
Imines and lactones derived from friedelanes and their cytotoxic activity.
(2018) Aguilar, Mariana Guerra de; Sousa, Grasiely Faria de; Evangelista, Fernanda Cristina Gontijo; Sabino, Adriano de Paula; Vieira Filho, Sidney Augusto; Duarte, Lucienir Pains
Friedelan-3-one (1) and friedelane-3,16-dione (2) isolated from leaves and branches of Maytenus robusta Reissek were subjected to structural modifications via nucleophilic addition to the carbonyl group and Baeyer-Villiger oxidation in order to synthesize potential cytotoxic compounds. The oximes friedelane-3-hydroxyimino (3) and 3-hydroxyiminofriedelan-16-one (4) together with the lactones friedelane-3,4-lactone (5) and 3,4-lactonefriedelan-16-one (6) were characterized by IR and NMR spectroscopic analyses. Compounds 4 and 6 are reported for the first time. Cytotoxic screening via MTT assay in human leukemia cell lines (THP-1 and K562) demonstrated no significant improvement of compounds 3-6 when compared to the starting materials. Only compounds 3 and 5 demonstrated an improvement against K562 cells. However, the same assay on ovar- ian and breast cancer cell lines (TOV-21G and MDA-MB-231) showed a reduction in the IC50 for compounds 4-6, indicating that ring A modifications may enhance the biological potential.
Lack of association between methylenetetrahydrofolate reductase C677T polymorphism, HPV infection and cervical intraepithelial neoplasia in Brazilian women.
(2019) Silva, Nayara Nascimento Toledo; Sabino, Adriano de Paula; Tafuri, Alexandre; Lima, Angélica Alves
Background: Cervical cancer has high prevalence and mortality rates in worldwide female population. Persistent infection by high-risk Human Papillomavirus (hr-HPV) is the main cause of this cancer. However, many environmental, genetical, and epigenetical cofactors can modulate viral infection and cervical carcinogenesis. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is a genetic factor that has been associated with many pathologies, including cancer. Nevertheless, studies with cervical cancer presented controversial results, and varied according to ethnicity. Thus, the aim of this study was to determine association between MTHFR C677T polymorphism, Human Papillomavirus (HPV) infection and cervical cancer. Methods: A case-control study was performed with 150 histological cervical samples. Case group were divided in Cervical Intraepithelial Neoplasia (CIN) grade I (n = 30), CIN II (n = 30), CIN III (n = 30), and Squamous Cervical Carcinoma (SCC) (n = 30). Control group was composed by 30 samples without lesion, presenting cervicitis. HPV detection was performed by conventional Polymerase Chain Reaction (PCR) with SPF primers set, and by real-time PCR specific for HPV 16 and hr-HPV. MTHFR C677T polymorphism was analyzed by PCR followed by Restriction Fragment Length Polymorphism (RFLP). Results: Frequency of MTHFR CC genotype was 72.7% (n = 109), CT 23.3% (n = 35) and TT 4.0% (n = 6). Polymorphic T allele frequency was 15.7%. No statistically significant association was observed between MTHFR C677T polymorphism and presence of pre-neoplastic or neoplastic cervical lesions. Similar frequencies of T allele was observed in control (23.3%) and cases (13.3%) groups (p = 0.174). In addition, there was no statistically significant association between MTHFR C677T polymorphism and viral infection, even considering hr-HPV or HPV 16 positivity. Conclusion: MTHFR C677T polymorphism was not associated with cervical cancer and HPV infection.
Synthesis, cytotoxic activity, and mode of action of new Santacruzamate A analogs.
(2018) Andrade, Silmara Nunes; Evangelista, Fernanda Cristina Gontijo; Seckler, Diego Eduardo Lima; Marques, Deisielly Ribeiro; Freitas, Tulio Resende; Nunes, Renata Rachide; Oliveira, Júlia Teixeira de; Ribeiro, Rosy Iara Maciel de Azambuja; Santos, Helio Batista dos; Thomé, Ralph Gruppi; Taranto, Alex Gutterres; Santos, Fabio Vieira dos; Viana, Gustavo Henrique Ribeiro; Freitas, Rossimiriam Pereira de; Humberto, Jorge Luiz; Sabino, Adriano de Paula
Breast and ovarian cancer are the most common cancers in women. Available cancer treatments, in general, have limited efficacy and frequent, undesirable side effects. Recently, scientists have focused on searching for new epigenetic modulators such as inhibitors of DNA methyltransferases and histone deacetylases (HDACs), with novel properties and selectivity. We report the synthesis of seven new analogs of Santacruzamate A. Molecular modeling showed that compounds 3–9 presented the best binding energies (kcal/mol) against HDAC4 compared to that of crystallographic ligand. The compounds were evaluated against MCF-7 and MDA-MB-231 (breast cancer), TOV-21G (ovarian adenocarcinoma), and WI-26VA4 (non-tumor lung fibroblasts) cells. Compound 5, the most potent and selective of the series, exhibited remarkably enhanced anticancer potency, with IC50 values for the tumor cells of 24.3–44.93 μM, compared with that of etoposide (12–18.57 μM) and doxorubicin (2.1–4.37 μM). Further investigation showed that compound 5 could promote DNA damage, increase the activity of caspases-3 and -9, and upregulate mRNA levels of p21, TP53, and BAK, suggesting apoptotic cell death of the tumor cells via the intrinsic pathway. This study demonstrated that synthetic analogs of santacruzamate A with zinc-linked groups are effective for improving both HDAC inhibition and antitumor activity.
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.