Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
1.
Nanomedicine ; 12(7): 2201-2214, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27262933

RESUMO

Glioblastoma multiforme (GBM) is the most common and aggressive primary neoplasm of the brain. Poor prognosis is mainly attributed to tumor heterogeneity, invasiveness, and drug resistance. microRNA-based therapeutics represent a promising approach due to their ability to inhibit multiple targets. In this work, we aim to restore the oncosuppressor activity of microRNA-34a (miR-34a) in GBM. We developed a cationic carrier system, dendritic polyglycerolamine (dPG-NH2), which remarkably improves miRNA stability, intracellular trafficking, and activity. dPG-NH2 carrying mature miR-34a targets C-MET, CDK6, Notch1 and BCL-2, consequently inhibiting cell cycle progression, proliferation and migration of GBM cells. Following complexation with dPG-NH2, miRNA is stable in plasma and able to cross the blood-brain barrier. We further show inhibition of tumor growth following treatment with dPG-NH2-miR-34a in a human glioblastoma mouse model. We hereby present a promising technology using dPG-NH2-miR-34a polyplex for brain-tumor treatment, with enhanced efficacy and no apparent signs of toxicity.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , MicroRNAs/farmacologia , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Portadores de Fármacos , Glioblastoma , Glicerol , Humanos , Polímeros
2.
Mol Cancer ; 12: 57, 2013 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-23758919

RESUMO

BACKGROUND: Cancer of unknown or uncertain primary is a major diagnostic and clinical challenge, since identifying the tissue-of-origin of metastases is crucial for selecting optimal treatment. MicroRNAs are a family of non-coding, regulatory RNA molecules that are tissue-specific, with a great potential to be excellent biomarkers. METHODS: In this study we tested the performance of a microRNA-based assay in formalin-fixed paraffin-embedded samples from 84 CUP patients. RESULTS: The microRNA based assay agreed with the clinical diagnosis at presentation in 70% of patients; it agreed with the clinical diagnosis obtained after patient management, taking into account response and outcome data, in 89% of patients; it agreed with the final clinical diagnosis reached with supplemental immunohistochemical stains in 92% of patients, indicating a 22% improvement in agreement from diagnosis at presentation to the final clinical diagnosis. In 18 patients the assay disagreed with the presentation diagnosis and was in agreement with the final clinical diagnosis, which may have resulted in the administration of more effective chemotherapy. In three out of four discordant cases in which supplemental IHC was performed, the IHC results validated the assay's molecular diagnosis. CONCLUSIONS: This novel microRNA-based assay shows high accuracy in identifying the final clinical diagnosis in a real life CUP patient cohort and could be a useful tool to facilitate administration of optimal therapy.


Assuntos
Carcinoma/diagnóstico , Carcinoma/genética , MicroRNAs/genética , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/genética , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
3.
Nucleic Acids Res ; 38(18): 6234-46, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20483914

RESUMO

MicroRNAs (miRNAs) are ∼22-nt long, non-coding RNAs that regulate gene silencing. It is known that many human miRNAs are deregulated in numerous types of tumors. Here we report the sequencing of small RNAs (17-25 nt) from 23 breast, bladder, colon and lung tumor samples using high throughput sequencing. We identified 49 novel miRNA and miR-sized small RNAs. We further validated the expression of 10 novel small RNAs in 31 different types of blood, normal and tumor tissue samples using two independent platforms, namely microarray and RT-PCR. Some of the novel sequences show a large difference in expression between tumor and tumor-adjacent tissues, between different tumor stages, or between different tumor types. We also report the identification of novel small RNA classes in human: highly expressed small RNA derived from Y-RNA and endogenous siRNA. Finally, we identified dozens of new miRNA sequence variants that demonstrate the existence of miRNA-related SNP or post-transcriptional modifications. Our work extends the current knowledge of the tumor small RNA transcriptome and provides novel candidates for molecular biomarkers and drug targets.


Assuntos
MicroRNAs/metabolismo , Neoplasias/genética , RNA Neoplásico/metabolismo , RNA não Traduzido/metabolismo , Humanos , MicroRNAs/química , Neoplasias/metabolismo , RNA Neoplásico/química , RNA não Traduzido/química , Análise de Sequência de RNA
4.
Cancer Res ; 70(20): 8077-87, 2010 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-20924108

RESUMO

Hepatocellular carcinoma (HCC) is generally a fatal disease due to a paucity of effective treatment options. The identification of oncogenic microRNAs that exert pleiotropic effects in HCC cells may offer new therapeutic targets. In this study, we have identified the human microRNA miR-191 as a potential target for HCC therapy. Inhibition of miR-191 decreased cell proliferation and induced apoptosis in vitro and significantly reduced tumor masses in vivo in an orthotopic xenograft mouse model of HCC. Additionally, miR-191 was found to be upregulated by a dioxin, a known liver carcinogen, and was found to be a regulator of a variety of cancer-related pathways. Our findings offer a preclinical proof of concept for miR-191 targeting as a rational strategy to pursue for improving HCC treatment.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Regiões 3' não Traduzidas/genética , Animais , Povo Asiático/genética , Carcinógenos/farmacologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Divisão Celular , Dioxinas/farmacologia , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Camundongos , MicroRNAs/efeitos dos fármacos , Modelos Animais , Modelos Genéticos , RNA Neoplásico/genética , RNA Neoplásico/isolamento & purificação , Transcrição Gênica/efeitos dos fármacos , Regulação para Cima , População Branca/genética
5.
PLoS One ; 3(9): e3148, 2008 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-18773077

RESUMO

BACKGROUND: Circulating nucleic acids (CNAs) offer unique opportunities for early diagnosis of clinical conditions. Here we show that microRNAs, a family of small non-coding regulatory RNAs involved in human development and pathology, are present in bodily fluids and represent new effective biomarkers. METHODS AND RESULTS: After developing protocols for extracting and quantifying microRNAs in serum and other body fluids, the serum microRNA profiles of several healthy individuals were determined and found to be similar, validating the robustness of our methods. To address the possibility that the abundance of specific microRNAs might change during physiological or pathological conditions, serum microRNA levels in pregnant and non pregnant women were compared. In sera from pregnant women, microRNAs associated with human placenta were significantly elevated and their levels correlated with pregnancy stage. CONCLUSIONS AND SIGNIFICANCE: Considering the central role of microRNAs in development and disease, our results highlight the medically relevant potential of determining microRNA levels in serum and other body fluids. Thus, microRNAs are a new class of CNAs that promise to serve as useful clinical biomarkers.


Assuntos
Biomarcadores/metabolismo , MicroRNAs/genética , Biomarcadores Tumorais , Sistema Livre de Células , DNA/sangue , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/fisiologia , Gravidez , Trimestres da Gravidez , RNA/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA