RESUMO
The objective of this study, a parallel study to global gene expression profiling, was to identify dysregulated microRNAs (miRNAs) associated with endometrioid endometrial adenocarcinoma (EEC), examine their correlation with clinico-pathological characteristics and identify predicted target genes of the dysregulated miRNAs. Using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), profiling of miRNA expression was performed in 30 EECs and 22 normal counterparts in which genome-wide gene expression had been previously profiled and reported. Clustering analysis identified 30 miRNAs which were significantly dysregulated in EEC. The expression of a sub-group of miRNAs was significantly correlated with clinico-pathological characteristics including stage, myometrial invasion, recurrence and lymph node involvement. By searching for predicted miRNA targets that were linked to the dysregulated genes previously identified, 68 genes were predicted as candidate targets of these 30 dysregulated miRNAs. miR-205 was significantly overexpressed in EECs compared with normal controls. After transfection of a miR-205 inhibitor, the expression of miR-205 in endometrial cancer cell line RL95-2 cells decreased whereas its predicted target gene, JPH4, showed increased protein expression. JPH4 seems to be a real miR-205 target in vitro and in vivo, and a candidate tumor suppressor gene in EEC. Based on this study in EEC, miRNAs predicted to be involved in tumorigenesis and tumor progression have been identified and placed in the context of the transcriptome of EEC. This work provides a framework on which further research into novel diagnosis and treatment of EEC can be focused.
Assuntos
Carcinoma Endometrioide/genética , Neoplasias do Endométrio/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Adulto , Idoso , Carcinoma Endometrioide/patologia , Linhagem Celular Tumoral , Neoplasias do Endométrio/patologia , Endométrio/citologia , Endométrio/patologia , Feminino , Hong Kong , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , RNA Neoplásico/genética , RNA Neoplásico/isolamento & purificação , Valores de ReferênciaRESUMO
We report three Japanese patients with glucose transporter type 1 deficiency syndrome (Glut1DS). Two patients had a normal erythrocyte 3-O-methylglucose (3OMG) uptake, one with a previously reported T295M substitution and the other with a novel 12-bp insertion at nt 1034-1035, ins CAGCAGCTGTCT. The third patient, with deficient 3OMG uptake, had a previously reported hot-spot mutation, R333W. All three patients responded to a ketogenic diet. All patients showed a significant improvement in ataxia, with blood beta-hydroxybutyrate (BOHB) levels ranging from 0.1 to 3mM. BOHB levels of at least 3mM were necessary to control seizures, and higher ketone levels are recommended to meet brain energy needs during development. FDG-PET scan, performed before and after a ketogenic diet in the R333W patient, did not change despite a clinical improvement. This clinical condition is treatable and early diagnosis is important.
Assuntos
Encefalopatias Metabólicas Congênitas/genética , Erros Inatos do Metabolismo dos Carboidratos/genética , Transportador de Glucose Tipo 1/deficiência , Ácido 3-Hidroxibutírico/sangue , Adulto , Arginina/genética , Encefalopatias Metabólicas Congênitas/sangue , Encefalopatias Metabólicas Congênitas/diagnóstico por imagem , Encefalopatias Metabólicas Congênitas/dietoterapia , Mapeamento Encefálico , Erros Inatos do Metabolismo dos Carboidratos/sangue , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico por imagem , Erros Inatos do Metabolismo dos Carboidratos/dietoterapia , Criança , Pré-Escolar , Feminino , Transportador de Glucose Tipo 1/genética , Humanos , Japão , Masculino , Metionina/genética , Mutação de Sentido Incorreto , Tomografia por Emissão de Pósitrons/métodos , Treonina/genética , Triptofano/genéticaRESUMO
Two new hexadeca-carboxy phthalocyanines have been synthesised and evaluated for their photodynamic activities; the zinc(II) analogue exhibits a high class-A scavenger-receptor mediated photocytotoxicity towards the J774 murine macrophage cell line.