Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 55
Filtrar
Mais filtros

País/Região como assunto
País de afiliação
Intervalo de ano de publicação
1.
Immunol Invest ; 51(4): 883-898, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33557640

RESUMO

BACKGROUND: Myocardial toxicity is a common side effect of doxorubicin (DOXO) therapy in breast cancer patients. We hypothesized that DOXO-induced cardiotoxicity may be related to the release of inflammatory cytokines in response to the treatment. This study aimed to assess changes in plasma levels of interleukin (IL)-1ß, IL-6, IL-10 and tumor necrosis factor (TNF) after chemotherapy and to correlate these levels with cardiac biomarkers and clinical data. METHODS: Sixty-four patients with breast cancer treated with DOXO were included. Twenty-two subjects (cases) developed cardiotoxicity until one year after the end of DOXO treatment. Cytokines and cardiac markers were evaluated before starting chemotherapy (T0), up to 7 days after the last infusion (T1) and 12 months after the last infusion (T2). RESULTS: Higher IL-10 levels were observed in the case group compared to controls at T1 (p = .006) and T2 (p = .046). The IL-1ß, IL-6 and TNF levels did not change during treatment in each group (p > .05), nor between the case and control groups. The IL-10 levels were higher at T1 than at T0 and T2 (p < .05 for both) in the cardiotoxicity group. A correlation between IL-10 and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at T0 and T2 in the cardiotoxicity group was observed (p = .048 and p = .004, respectively). CONCLUSION: Our study demonstrated that DOXO induced an increase in plasma IL-10 levels in patients who presented cardiotoxicity after treatment, which correlated with NT-proBNP levels.


Assuntos
Neoplasias da Mama , Cardiotoxicidade , Interleucina-10 , Biomarcadores , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/etiologia , Doxorrubicina/efeitos adversos , Feminino , Seguimentos , Humanos , Interleucina-10/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue
2.
J Pediatr ; 237: 298-301.e1, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34216632

RESUMO

We evaluated neurologic complications following noncongenital Zika virus infection in 11 children who presented with central nervous system signs. Zika virus RNA was detected by real-time reverse transcription-polymerase chain reaction in cerebrospinal fluid. Approximately one-quarter of patients required antiepileptic medication in follow-up, and 2 children progressed to learning difficulties or developmental delay.


Assuntos
Deficiências do Desenvolvimento/virologia , Deficiências da Aprendizagem/virologia , Doenças do Sistema Nervoso/virologia , Infecção por Zika virus/complicações , Anticonvulsivantes/uso terapêutico , Brasil , Criança , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico , Eletroencefalografia , Feminino , Hospitalização , Humanos , Lactente , Deficiências da Aprendizagem/diagnóstico , Masculino , Doenças do Sistema Nervoso/diagnóstico , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Zika virus/isolamento & purificação , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/psicologia
3.
Exp Mol Pathol ; 116: 104520, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32828740

RESUMO

One of the models that best explains the cellular heterogeneity observed in central nervous system (CNS) tumors is the presence of cancer stem cells (CSCs). CSCs can originate from differentiated adult cells that return to an undifferentiated stage through the mechanism known as epithelial-mesenchymal transition (EMT). In this paper, we evaluated cellular and molecular heterogeneity and the participation of the epithelial-mesenchymal transition (EMT) in glioblastoma (U-87 MG and LN-18) and neuroblastoma (KELLY and IMR-32) cell lines cultured in monolayer (2D) and neurosphere (CSC enrichment- 3D) models. For this, after treatment with cisplatin, we studied different cell subpopulations by immunophenotyping using neural stem cell/progenitor markers (ALDH, CD24, CD56, and CD133), mesenchymal stem cell markers (CD73, CD90, CD105, and CD146) and hematopoietic markers (CD14, CD19, CD34, CD45, and HLA-DR) and mRNA expression profiles of genes related to EMT, such as ZEB1, TWIST1, TGFB1, STAT3, and lncRNA HOTAIR. In addition, we evaluated the growth capacity of residual cells when treated with cisplatin using the chorioallantoic membrane (CAM) model to study disease relapse. After treatment with cisplatin, we found that the expression of STAT3 and TGFB1 genes markedly increased in the neurosphere of the IMR-32 cell line, and TWIST1 was upregulated in the neurosphere of LN-18. Only the nontreated monolayer of LN-18, KELLY, and IMR-32 amplified the lncRNA HOTAIR. The IMR-32 cell line exhibited an enrichment of CD24+/ALDH+ and this cell subset decreased after cisplatin treatment. We observed the loss of CD146+/CD73+ cell subpopulations in U-87 MG monolayer and neurosphere models, after cisplatin treatment, while in LN-18 monolayer cisplatin-treated cells, CD73+/CD90+ cell subpopulations increased. Neuroblastoma cell lines showed CD14+/HLA-DR- cell subpopulations representative of myeloid-derived suppressor cells (MDSCs). Tumors generated from residual cells, after exposure to cisplatin, grafted on CAM showed patterns of organization different from those of the controls. Thus, our findings strongly supported the idea that definitions of tumor phenotypic characteristics may help to establish better therapeutic strategies for the development of new drug targets.


Assuntos
Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Cisplatino/farmacologia , Glioblastoma/tratamento farmacológico , Neuroblastoma/tratamento farmacológico , Técnicas de Cultura de Células , Diferenciação Celular/genética , Linhagem Celular Tumoral , Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Membrana Corioalantoide/efeitos dos fármacos , Membrana Corioalantoide/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Antígenos Comuns de Leucócito/genética , Células-Tronco Mesenquimais/efeitos dos fármacos , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Neuroblastoma/genética , Neuroblastoma/patologia , Proteínas Nucleares/genética , Fator de Crescimento Transformador beta1/genética , Proteína 1 Relacionada a Twist/genética
4.
Planta Med ; 86(17): 1286-1297, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32797466

RESUMO

Rosmarinic acid, a plant-derived compound with antiangiogenic activity, can be applied for the treatment of ocular diseases related to neovascularization, such as diabetic retinopathy, macular edema, and age-related macular degeneration. These diseases represent the leading causes of blindness worldwide if they are not properly treated. Intravitreal devices allow for localized drug delivery to the posterior segment, increasing the drug bioavailability and promoting extended release, thus, reducing side effects and enhancing the patient's compliance to the treatment. In this work, rosmarinic acid-loaded poly lactic-co-glycolic acid intraocular implants were developed with a view for the treatment of ocular neovascularization. Physical-chemical, biocompatibility, and safety studies of the implants were carried out in vitro and in vivo as well as an evaluation of the antiangiogenic activity in a chorioallantoic membrane assay. Data obtained showed that rosmarinic acid released from the implants was quantified in the vitreous for 6 weeks, while when it was in the solution formulation, after 24 h, no drug was found in the vitreous. The delivery device did not show any sign of toxicity after clinical evaluation and in electroretinographic findings. Histological analysis showed normal eye tissue. Rosmarinic acid released from implants reduced 30% of new vessel's formation. The intravitreal implant successfully allowed for the prolonged release of rosmarinic acid, was safe to rabbits eyes, and demonstrated activity in vessel reduction, thus demonstrating potential in preventing neovascularization in ophthalmic diseases.


Assuntos
Depsídeos , Corpo Vítreo , Animais , Cinamatos , Depsídeos/farmacologia , Humanos , Injeções Intravítreas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos , Ácido Rosmarínico
5.
Mem Inst Oswaldo Cruz ; 115: e190498, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609280

RESUMO

BACKGROUND: Biomphalaria glabrata snails are widely distributed in schistosomiasis endemic areas like America and Caribe, displaying high susceptibility to infection by Schistosoma mansoni. After the availability of B. glabrata genome and transcriptome data, studies focusing on genetic markers and small non-coding RNAs have become more relevant. The small RNAs have been considered important through their ability to finely regulate the gene expression in several organisms, thus controlling the functions like cell growth, metabolism, and susceptibility/resistance to infection. OBJECTIVE: The present study aims on identification and characterisation of the repertoire of small non-coding RNAs in B. glabrata (Bgl-small RNAs). METHODS: By using small RNA sequencing, bioinformatics tools and quantitative reverse transcription polymerase chain reaction (RT-qPCR), we identified, characterised, and validated the presence of small RNAs in B. glabrata. FINDINGS: 89 mature miRNAs were identified and five of them were classified as Mollusk-specific. When compared to model organisms, sequences of B. glabrata miRNAs showed a high degree of conservation. In addition, several target genes were predicted for all the mature miRNAs identified. Furthermore, piRNAs were identified in the genome of B. glabrata for the first time. The B. glabrata piRNAs showed strong conservation of uridine as first nucleotide at 5' end, besides adenine at 10th position. Our results showed that B. glabrata has diverse repertoire of circulating ncRNAs, several which might be involved in mollusk susceptibility to infection, due to their potential roles in the regulation of S. mansoni development. MAIN CONCLUSIONS: Further studies are necessary in order to confirm the role of the Bgl-small RNAs in the parasite/host relationship thus opening new perspectives on interference of small RNAs in the organism development and susceptibility to infection.


Assuntos
Biomphalaria/genética , Biomphalaria/parasitologia , MicroRNAs/genética , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/genética , Esquistossomose mansoni/fisiopatologia , Animais , Predisposição Genética para Doença/genética , Sequenciamento de Nucleotídeos em Larga Escala , Interações Hospedeiro-Parasita , RNA Interferente Pequeno , Reação em Cadeia da Polimerase Via Transcriptase Reversa
6.
Eur Biophys J ; 48(7): 673-684, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485678

RESUMO

Triple negative breast cancer (TNBC) is a highly heterogeneous disease, which influences the therapeutic response and makes difficult the discovery of effective targets. This heterogeneity is attributed to the presence of breast cancer stem cells (BCSCs), which determines resistance to chemotherapy and subsequently disease recurrence and metastasis. In this context, this work aimed to evaluate the morphological and phenotypic cellular heterogeneity of two TNBC cell lines cultured in monolayer and tumorsphere (TS) models by fluorescence and electron microscopy and flow cytometry. The BT-549 and Hs 578T analyses demonstrated large phenotypic and morphological heterogeneity between these cell lines, as well as between the cell subpopulations that compose them. BT-549 and Hs 578T are heterogeneous considering the cell surface marker CD44 and CD24 expression, characterizing BCSC mesenchymal-like cells (CD44+/CD24-), epithelial cells (CD44-/CD24+), hybrid cells with mesenchymal and epithelial features (CD44+/CD24+), and CD44-/CD24- cells. BCSC epithelial-like cells (ALDH+) were found in BT-549, BT-549 TS, and Hs 578T TS; however, only BT-549 TS showed a high ALDH activity. Ultrastructural characterization showed the heterogeneity within and among BT-549 and Hs 578T in monolayer and TS models being formed by more than one cellular type. Further, the mesenchymal characteristic of these cells is demonstrated by E-cadherin absence and filopodia. It is well known that tumor cell heterogeneity can influence survival, therapy responses, and the rate of tumor growth. Thus, molecular understanding of this heterogeneity is essential for the identification of potential therapeutic options and vulnerabilities of oncological patients.


Assuntos
Células-Tronco Neoplásicas/ultraestrutura , Fenótipo , Neoplasias de Mama Triplo Negativas/patologia , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Humanos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia
7.
Exp Cell Res ; 363(2): 283-290, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29352988

RESUMO

The cancer stem cell (CSC) concept is currently employed to explain the mechanism of multidrug resistance that is implicated in the reduced efficacy of many chemotherapeutic agents, consequently leading to metastatic spread and disease relapse. We searched for potential predictive markers of doxorubicin (DOX) resistance in breast cancer stem cells (BCSCs) of the BT-549 human triple-negative breast cancer (TNBC) cell line classified as a claudin-low subtype. In this study, we show that BT-549 presents a BCSCs-like subset determined by a CD44+/high/CD24-/low/ALDH1+ phenotype. The CD44+/high/CD24-/low/ALDH+ BCSCs-like subset presented the downregulation of a majority of the genes analyzed (64 genes), and only 3 genes were upregulated after DOX treatment. Among the upregulated genes, MAPK3, PRKCZ and STAT3, STAT3 presented a higher level of upregulation in the DOX-treated CD44+/high/CD24-/low/ALDH+ BCSCs-like subset. The identification of biomarkers that predict antitumor responses is at the top of cancer research priorities. STAT3 was highlighted as a molecular signature in the CD44+/high/CD24-/low/ALDH1+ BCSCs-like subset obtained from the TNBC BT-549 cell line related to DOX resistance. A majority of the evaluated genes in the EGF pathway appear to be not associated with DOX resistance, as observed in the CD44+/high/CD24-/low/ALDH1+ BCSCs-like subset.


Assuntos
Antineoplásicos/farmacologia , Biomarcadores/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Antígeno CD24/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia
8.
Bioorg Med Chem ; 25(3): 1153-1162, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28041802

RESUMO

An efficient method for the synthesis of quinolines using microwave irradiation was developed providing 28 quinolines with good yields. The reaction procedures are environmentally friendly, convenient, mild and of easy work-up. Quinolines were evaluated for their antifungal, anticancer and antioxidant properties and exhibited high activities in all tests performed.


Assuntos
Antifúngicos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Micro-Ondas , Quinolinas/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/química , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Quinolinas/síntese química , Quinolinas/química , Relação Estrutura-Atividade
9.
Mar Drugs ; 12(8): 4361-78, 2014 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-25089949

RESUMO

Cancer continues to be one of the most important health problems worldwide, and the identification of novel drugs and treatments to address this disease is urgent. During recent years, marine organisms have proven to be a promising source of new compounds with action against tumoral cell lines. Here, we describe the synthesis and anticancer activity of eight new 3-alkylpyridine alkaloid (3-APA) analogs in four steps and with good yields. The key step for the synthesis of these compounds is a Williamson etherification under phase-transfer conditions. We investigated the influence of the length of the alkyl chain attached to position 3 of the pyridine ring on the cytotoxicity of these compounds. Biological assays demonstrated that compounds with an alkyl chain of ten carbon atoms (4c and 5c) were the most active against two tumoral cell lines: RKO-AS-45-1 and HeLa. Micronucleus and TUNEL assays showed that both compounds are mutagenic and induce apoptosis. In addition, Compound 5c altered the cellular actin cytoskeleton in RKO-AS-45-1 cells. The results suggest that Compounds 4c and 5c may be novel prototype anticancer agents.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Piridinas/química , Piridinas/farmacologia , Citoesqueleto de Actina/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Células HeLa , Humanos , Relação Estrutura-Atividade
10.
Arch Gynecol Obstet ; 289(5): 1061-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24190693

RESUMO

OBJECTIVE: This study assesses TRAIL-R2 (TNF-related apoptosis-inducing ligand receptor 2) and BCL2 (B cell CLL/lymphoma 2) expression as well as CpG island methylation within the TRAIL-R2 promoter in ovarian serous tumors and primary and metastatic serous EOC (epithelial ovarian cancer). METHODS: RNA and DNA were obtained from women with normal ovarian tissues (n = 18), ovarian serous cystadenoma tumors (n = 11) and serous EOC (n = 16) using Trizol®. Quantitative PCR was performed to quantify the relative levels of TRAIL-R2 and BCL2. The methylation frequency of the TRAIL-R3 promoter was assessed using a methylation-specific PCR assay after DNA bisulfite conversion. Differences between the groups were evaluated using the χ (2), Mann-Whitney U or Kruskal-Wallis tests, as indicated. RESULTS: We identified TRAIL-R2 and BCL2 mRNA expressed in all ovarian tumor groups, and there were significant differences between the groups. Both genes had low expression levels in ovarian serous cystadenoma and primary EOC tumors when compared with metastatic EOC. Methylation of the TRAIL-R2 promoter was frequently observed in all groups; however, there were no statistically significant associations. CONCLUSIONS: Primary EOC is associated with lower TRAIL-R2 and BCL2 expression levels, while metastatic EOC is associated with higher expression of these genes. Promoter DNA methylation was not related to this finding, suggesting there are other mechanisms involved in transcriptional control.


Assuntos
Cistadenoma Seroso/genética , Metilação de DNA , Epigênese Genética , Expressão Gênica , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Reguladoras de Apoptose/genética , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Estudos Prospectivos , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Estatísticas não Paramétricas
11.
Diagnostics (Basel) ; 13(9)2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37174944

RESUMO

Breast cancer is the most common cancer and the most frequent cause of death in women. Doxorubicin, an anthracycline, is an important drug due to its efficacy in treating solid cancers, especially breast cancer. However, this drug is often responsible for cardiotoxicity that may affect more than 25% of patients. This study aimed to evaluate the red cell distribution width (RDW) in women with breast cancer to monitor adverse events associated with the use of doxorubicin. A prospective study of 80 women with breast malignancy undergoing neoadjuvant doxorubicin-based chemotherapy was conducted. The patients were evaluated at baseline (T0), just after the last cycle of chemotherapy with doxorubicin (T1), and 1 year after the treatment (T2). There was a significant increase over the time points for the RDW (p < 0.001). There was a negative correlation between the RDW and C-reactive protein (CRP) levels at T1. The RDW did not show a significant difference between the groups classified according to cardiotoxicity. Based on these results, the RDW is a cost-effective test that shows a relationship with the doxorubicin response, but not with cardiotoxicity. It is a potential biomarker to evaluate patients with breast cancer after they receive chemotherapy with doxorubicin.

12.
Rev Bras Ginecol Obstet ; 45(2): 74-81, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36977404

RESUMO

OBJECTIVE: The present study evaluated the profile of germline mutations present in patients who underwent genetic counseling for risk assessment for breast cancer (BC), ovarian cancer (OC), and endometrial cancer (EC) with a possible hereditary pattern. METHODS: Medical records of 382 patients who underwent genetic counseling after signing an informed consent form were analyzed. A total of 55.76% of patients (213/382) were symptomatic (personal history of cancer), and 44.24% (169/382) were asymptomatic (absence of the disease). The variables analyzed were age, sex, place of birth, personal or family history of BC, OC, EC, as well as other types of cancer associated with hereditary syndromes. The Human Genome Variation Society (HGVS) nomenclature guidelines were used to name the variants, and their biological significance was determined by comparing 11 databases. RESULTS: We identified 53 distinct mutations: 29 pathogenic variants, 13 variants of undetermined significance (VUS), and 11 benign. The most frequent mutations were BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T, and BRCA2 c.2T> G. Furthermore, 21 variants appear to have been described for the first time in Brazil. In addition to BRCA1/2 mutations, variants in other genes related to hereditary syndromes that predispose to gynecological cancers were found. CONCLUSION: This study allowed a deeper understanding of the main mutations identified in families in the state of Minas Gerais and demonstrates the need to assess the family history of non-gynecological cancer for risk assessment of BC, OC, and EC. Moreover, it is an effort that contributes to population studies to evaluate the cancer risk mutation profile in Brazil.


OBJETIVO: O presente estudo avaliou o perfil de mutações germinativas presentes em pacientes submetidas a aconselhamento genético para avaliação de risco para câncer de mama (CM), câncer de ovário (OC) e câncer de endométrio (CE) com possível padrão hereditário. MéTODOS: Foram analisados os prontuários de 382 pacientes que realizaram aconselhamento genético após consentimento informado. Um total de 55,76% dos pacientes (213/382) eram sintomáticos (história pessoal de câncer), e 44,24% (169/382) eram assintomáticos (ausência da doença). As variáveis analisadas foram idade, sexo, naturalidade, história pessoal ou familiar de CM, OC, CE bem como outros tipos de câncer associados a síndromes hereditárias. As diretrizes de nomenclatura da Human Genome Variation Society (HGVS) foram usadas para nomear as variantes e seu significado biológico foi determinado pela comparação de 11 bancos de dados. RESULTADOS: Identificamos 53 mutações distintas: 29 variantes patogênicas, 13 variantes de significado indeterminado e 11 benignas. As mutações mais frequentes foram BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T e BRCA2 c.2T > G. Além disso, 21 variantes parecem ter sido descritas pela primeira vez no Brasil. Além das mutações BRCA1/2, foram encontradas variantes em outros genes relacionados a síndromes hereditárias que predispõem a cânceres ginecológicos. CONCLUSãO: Este estudo permitiu conhecer melhor as principais mutações identificadas nas famílias do estado de Minas Gerais e demonstra a necessidade de avaliar a história familiar de câncer não ginecológico para avaliação do risco de CM, OC e CE. Além disso, é um esforço que contribui com estudos populacionais para avaliar o perfil de mutações de risco para câncer no Brasil.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Feminino , Humanos , Brasil/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Aconselhamento Genético , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia
13.
Plants (Basel) ; 12(21)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37960102

RESUMO

Soybean is one of the most widely grown crops in the world and technologies are increasingly needed to increase productivity without impacting environmental degradation. In this context, the aim was to evaluate the action of forage plants of the genus Brachiaria sp. in crop-livestock integration on physical soil, agronomic and environmental aspects of soybean cultivation. The experiment was conducted in a subdivided plot design with seven integrated systems corresponding to the previous cultivation of Paiaguas palisadegrass, Xaraes palisadegrass and Ruziziensis grass in monocropping and intercropped with maize, as well as maize in monocropping. In the subplots, two grass management systems were evaluated: free growth and a grazing simulation cut. The bulk density and least limiting water range were assessed using soil samples and, after the pastures were desiccated when the soybean crop was planted, straw decomposition and plantability. A soil physics diagnosis by the bulk density and least limiting water range showed that the Paiaguas palisadegrass and Xaraes palisadegrass improved the soil environment due to biological soil loosening. The remaining mulch biomass did not affect soybean sowing and the adoption of Brachiaria sp. grass in the off-season, in addition to contributing to the provision of environmental services, and did not compromise grain productivity in succession.

14.
Gynecol Oncol ; 126(2): 268-73, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22555108

RESUMO

OBJECTIVE: To assess the expression of TRAIL-R3 and the methylation of a CpG island within the TRAIL-R3 promoter both in cystadenoma tumors and primary and metastatic epithelial ovarian carcinoma (EOC). METHODS: RNA was obtained from women with normal ovarian (NO) tissues (n=18), ovarian serous cystadenoma tumors (n=11) and EOC (n=16) using Trizol. Quantitative PCR (qRT-PCR) was performed to quantify the relative levels of TRAIL-R3. The methylation frequency of the CpG island in the TRAIL-R3 promoter was assessed using the methylation-specific PCR (MSP) assay after DNA bisulfite conversion. The differences between the groups were evaluated using the chi-square, Student's t, ANOVA, Mann-Whitney U, Wilcoxon or Kruskal-Wallis tests as indicated. The survival rates were calculated using the Kaplan-Meier method. RESULTS: Cystadenoma and metastatic EOC tumors expressed significantly more TRAIL-R3 mRNA than primary EOC tumors. Methylation of the TRAIL-R3 promoter was absent in NO tissues, while hemimethylation of the TRAIL-R3 promoter was frequently found in the neoplasia samples with 45.4% of the cystadenoma tumors, 8.3% of the primary EOC samples and 11.1% of the metastatic EOC samples showing at least partial methylation (p=0.018). Neither the expression of TRAIL-R3 nor alterations in the methylation profile were associated to cumulative progression-free survival or the overall survival in EOC patients. CONCLUSIONS: Primary EOC is associated to a lower TRAIL-R3 expression, which leads to a better understanding of the complex disease and highlighting potential therapeutic targets. Promoter DNA methylation was not related to this finding, suggesting the presence of other mechanisms to transcriptional control.


Assuntos
Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Receptores Chamariz do Fator de Necrose Tumoral/biossíntese , Receptores Chamariz do Fator de Necrose Tumoral/genética , Apoptose/fisiologia , Linhagem Celular Tumoral , Cistadenocarcinoma Seroso/patologia , Metilação de DNA , Intervalo Livre de Doença , Epigenômica , Feminino , Proteínas Ligadas por GPI/biossíntese , Proteínas Ligadas por GPI/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Estudos Prospectivos , Membro 10c de Receptores do Fator de Necrose Tumoral
15.
Acta Histochem ; 124(2): 151849, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35033934

RESUMO

The complexity of different components of tumor stroma poses huge challenges for therapies targeting the neuroblastoma (NB) microenvironment. The present study aimed to evaluate platinum-based response in IMR-32 neuroblastoma cell line cultured in monolayer (2D) and neurosphere (3D) models. For this, we evaluated mRNA expression of heat shock proteins HSPA1A, HSPB1, TRAP1, HSPA1AL, HSPD1, and DNA damage repair gene ERCC1. After treatment, residual cells were grafted on CAM (chicken chorioallantoic membrane) to evaluate the growth capability and histological paraffin sections were made to assess Ki-67 and HER-2 proteins by immunofluorescence. Our results showed that cisplatin induces mRNA downregulation of Heat Shock Proteins and ERCC1 in IMR-32 cells cultured in 2D or 3D models. In addition, the cisplatin-treatment approach increased HER-2 expression in residual IMR-32 cells grafted on the CAM. Therefore, these insights provide many advances in neuroendocrine tumor biology and knowledge about cisplatin-response in neuroblastoma.


Assuntos
Antineoplásicos , Células-Tronco Neurais , Neuroblastoma , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular , Linhagem Celular Tumoral , Cisplatino/farmacologia , Proteínas de Choque Térmico HSP90 , Humanos , Recidiva Local de Neoplasia , Neuroblastoma/tratamento farmacológico , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Microambiente Tumoral
16.
Acta Histochem ; 124(1): 151821, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34861601

RESUMO

The identification of the best reference gene is a critical step to evaluate the relative change in mRNA expression of a target gene by RT-qPCR. In this work, we evaluated nineteen genes of different functional classes using Real Time Human Reference Gene Panel (Roche Applied Sciences), to identify the internal housekeeping genes (HKGs) most suitable for gene expression normalization data in human cell lines. Normal cell lines CCD-19LU (lung fibroblast), HEK-293 (epithelial cell of embryonic kidney), WI-26 VA4 (lung fibroblast), and human cancer cells, BT-549 (breast cancer), Hs 578T (breast cancer), MACL-1 (breast cancer), HeLa (cervical carcinoma), U-87 MG (glioblastoma/astrocytoma), RKO-AS45-1 (colorectal carcinoma), and TOV-21G (ovarian adenocarcinoma) were cultivated according to manufacturer's protocol. Twelve candidate reference genes were commonly expressed in five cell lines (CCD-19Lu, HEK-293, RKO-AS45-1, TOV-21G, and U-87 MG). To verify the expression stability, we used the RefFinder web tool, which integrates data from the computational programs Normfinder, BestKeeper, geNorm, and the comparative Delta-Ct method. The ACTB was the most stable reference gene to the CCD-19Lu and HEK-293 cells. The best combination of HKGs for the RKO-AS45-1 and TOV-21G cell lines were B2M/GAPDH and PBGD/B2M, respectively. For the U-87 MG cells, GAPDH and IPO8 were the most suitable HKGs. Thus, our findings showed that it is crucial to use the right HKGs to precise normalize gene expression levels in cancer studies, once a suitable HKG for one cell type cannot be to the other.


Assuntos
Adenocarcinoma , Genes Essenciais , Genes Essenciais/genética , Células HEK293 , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Padrões de Referência
17.
Cardiovasc Toxicol ; 22(7): 655-662, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35524907

RESUMO

Cardiovascular toxicity is the main adverse effect of Doxorubicin (DOX) in cancer patients. microRNAs (miRNAs) are promising biomarkers to identify cardiac injury induced by DOX in breast cancer patients during the subclinical phase. Using RT-qPCR, we compared the expression of circulating miR-208a5p, miR-133a, miR-499a5p, miR-15a, miR-133b, and miR-49a3p in serum samples from DOX-induced cardiotoxicity (case) compared to the non-cardiotoxicity group (control). To further explore the potential roles of these circulating miRNA in cardiotoxicity, we searched the miRTarBase for experimentally validated miRNA-target interactions and performed a functional enrichment analysis based on those interactions. miR-133a was significantly upregulated in case compared to control group. The most relevant pathway regulated by miR-133a was ErbB2 signaling, whose main genes involved are EGFR, ERBB2, and RHOA, which are possibly downregulated by miR133a. The other miRNAs did not show significant differential expression when compared on both groups. The data suggest that miR-133a is associated with DOX-based cardiotoxicity during chemotherapy in breast cancer patients through ErbB2 signaling pathway. Moreover, miR-133a may be a future marker of DOX-induced cardiotoxicity in women with breast cancer.


Assuntos
Neoplasias da Mama , MicroRNAs , Biomarcadores , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Cardiotoxicidade/genética , Doxorrubicina/efeitos adversos , Feminino , Humanos , MicroRNAs/metabolismo , Transdução de Sinais
18.
Artigo em Inglês | MEDLINE | ID: mdl-35647524

RESUMO

Uveitis is a group of sight-threatening ocular inflammatory disorders, whose mainstay of therapy is associated with severe adverse events, prompting the investigation of alternative treatments. The peptide melittin (MEL) is the major component of Apis mellifera bee venom and presents anti-inflammatory and antiangiogenic activities, with possible application in ophthalmology. This work aims to investigate the potential of intravitreal MEL in the treatment of ocular diseases involving inflammatory processes, especially uveitis. Safety of MEL was assessed in retinal cells, chick embryo chorioallantoic membranes, and rats. MEL at concentrations safe for intravitreal administration showed an antiangiogenic activity in the chorioallantoic membrane model comparable to bevacizumab, used as positive control. A protective anti-inflammatory effect in retinal cells stimulated with lipopolysaccharide (LPS) was also observed, without toxic effects. Finally, rats with bacille Calmette-Guerin- (BCG) induced uveitis treated with intravitreal MEL showed attenuated disease progression and improvement of clinical, morphological, and functional parameters, in addition to decreased levels of proinflammatory mediators in the posterior segment of the eye. These effects were comparable to the response observed with corticosteroid treatment. Therefore, MEL presents adequate safety profile for intraocular administration and has therapeutic potential as an anti-inflammatory and antiangiogenic agent for ocular diseases.

19.
Acta Histochem ; 123(6): 151768, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34403847

RESUMO

Despite aggressive therapy, most patients with brain tumors present disease relapse due to the cellular and molecular nature of these tumors. One of the models that best explains the heterogeneity observed in CNS tumors is the presence of cancer stem cells (CSCs). In this paper, we evaluated platinum-based response in brain tumor U-87 MG, LN-18, and KELLY cell lines cultured in monolayer (2D) and neurosphere (CSC enrichment- 3D) models. We evaluated mRNA expression of heat shock proteins (HSPA1A, HSPB1, HSPA1AL, TRAP1, and HSPD1), and DNA repair gene ERCC1. Changes in cell cycle and glycosylation profile were assessed by flow cytometry. After treatment with cisplatin, we found that the mRNA expression of HSPs markedly increased in the U-87 MG and LN-18 neurosphere cells. In KELLY monolayer cells, cisplatin induced upregulation of all genes. In KELLY neurosphere cells, only the HSPA1A, HSPB1, TRAP1, and HSPD1 genes were upregulated. The proportion of cells in the G0/G1 phase was significantly higher in U-87 MG neurosphere cisplatin-treated cells. A trend towards a greater proportion of cells in the S phase of U-87 MG monolayer cisplatin-treated cells was also observed. On the other hand, a significant decrease in the number of cells in the S phase and an increase in G2/M was observed in LN-18 monolayer cisplatin-treated cells. Glycosylation analysis using lectins showed a higher surface binding for PNA in the U-87 MG treated monolayer and a lower binding for Concanavalin A in the treated neurospheres. The binding of Isolectin GS-IB4, GSII, and SBA in KELLY monolayer cisplatin-treated cells was lower whereas the proportion of cells labeled with Concanavalin A was higher. In the KELLY neurosphere cisplatin-treated cells, the binding of Concanavalin A was lower than nontreated cells. Thus, our findings strongly supported the idea that definitions of phenotypic characteristics may help to establish better therapeutic strategies for brain tumors.


Assuntos
Cisplatino/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/metabolismo , Proteínas de Neoplasias/biossíntese , Esferoides Celulares/metabolismo , Regulação para Cima/efeitos dos fármacos , Técnicas de Cultura de Células , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Glioblastoma/patologia , Humanos , Esferoides Celulares/patologia
20.
Pathog Glob Health ; 115(7-8): 476-482, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34223795

RESUMO

The aim was to assess neurological complications in children with an invasive neurological disease by dengue virus (DENV) and the time to resolve symptoms after hospital discharge. A prospective study was conducted at a referral hospital for infectious diseases in Brazil between March 2014 and July 2019. All children hospitalized with neurologic manifestations and DENV RNA detected by real-time reverse transcription-polymerase chain reaction (RT-qPCR) in cerebrospinal fluid (CSF) were followed up until complete resolution of neurological complications. On average, they were followed up for 16 months. Among 56 DENV-positive children, 39% had some neurologic complications after hospital discharge and found that 19.6% were discharged with anticonvulsants due to seizures, 10.7% developed motor complications (e.g. muscle weakness, paresis, ataxia, and walking disability), 5.4% had headaches, and 14.3% had sleep disorders. Among the 56 children, only three had a clinical diagnosis of dengue because the symptoms are nonspecific and 35% showed no change in cerebrospinal fluid (CSF). The average time to resolve complications was 5.9 months (ranging from 1 m to 32 m). These results should alert physicians to the difficulties of a clinical diagnosis of an infection that causes neurological complications after discharge in a significant number of children. RT-qPCR's etiological diagnosis of DENV infection enabled better clinical follow-up for early intervention in children with neurological complications.


Assuntos
Vírus da Dengue , Dengue , Criança , Dengue/complicações , Dengue/diagnóstico , Seguimentos , Humanos , Imunoglobulina M , Estudos Prospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA