RESUMO
BACKGROUND: Mucopolysaccharidosis type II (MPS II) or Hunter syndrome is a rare X-linked recessive genetic disease resulting from deficient activity of the iduronate-2-sulfatase(IDS) enzyme and the accumulation of glycosaminoglycans in almost all cells, tissues and organs, which makes viscera function impaired.This study retrospectively analyzed the clinical characteristics, leukocyte IDS activity and mutations in the IDS gene of 30 Chinese children with MPS II. METHODS: Whole-exome sequencing (WES) was performed on samples of the 30 patients. RESULTS: A total of 25 mutations were identified in the IDS genes including 16 previously reported and 9 novel mutations (6 frameshift: c.815-818dupAACG, c.1453dupA, c.1270-1271delGT, c.1484-1485insTA, c.854delA, c.12_13delCC;3missense: c.325 T > G, c.140 T > C, c.248 T > G).The computer simulations of the protein structure analysis of the novel missense mutations showed these amino acid replacements (W109G tryptophan replaced by the glycine, L47P leucine replaced by the proline, V83G valine replaced by glycine) near the active site of IDS protein sulfatase domain and would cause a severe impairment of protein structure and function. CONCLUSIONS: Our study expands the spectrum of MPS II genotype, provides new insights into the molecular mechanisms of MPS II, and contributes to future studies of genotype-phenotypic associations to estimate prognosis and develop new treatment regimens.
Assuntos
Glicoproteínas/genética , Iduronato Sulfatase , Mucopolissacaridose II , Povo Asiático/genética , Criança , China , Humanos , Iduronato Sulfatase/genética , Mucopolissacaridose II/genética , Mutação , Estudos RetrospectivosRESUMO
The successful treatment of most cancers depends on early detection. Tumor mRNA as a specific marker provides new avenues to monitor tumor progression in the early stages and assesses response to treatment. However, single tumor mRNA testing usually yields "false positive" results because cancer is associated with multiple tumor mRNA. It is indispensable to develop simple and effective approaches for the detection of multiple tumor mRNA. In this study, we used a combination of tumor-specific mRNA markers to avoid the inherent limitations associated with the single-marker technique. A gold nanoparticle (AuNP) was assembled with a bi-molecular beacon (bi-MB), and termed AuNP/bi-MB, which simultaneously targeted to two types of tumor mRNA in breast cancer cells. This imaging agent could prevent effectively false positive results and provide comprehensive and dependable information for the early detection of cancer. It would be beneficial to identify the stage of tumor progression and assess treatment decisions with the real-time detection of the relative expression levels of tumor mRNA in cancer cells. This strategy would offer an appealing approach toward the early detection of cancer by using multianalysis of tumor mRNA.
Assuntos
Biomarcadores Tumorais/química , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/química , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Ouro/química , Nanopartículas Metálicas/química , Imagem Molecular/métodos , Neoplasias/química , Neoplasias/patologia , Sondas de Oligonucleotídeos/química , Sondas de Oligonucleotídeos/metabolismo , RNA Mensageiro/química , Sequência de Bases , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Feminino , Fluorescência , Humanos , Sondas de Oligonucleotídeos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
We demonstrate a tumor mRNA-dependent drug carrier for controlled release of doxorubicin (Dox) and intracellular imaging based on gold nanoparticle-molecular beacon. Fluorescent Dox is released effectively and induces apoptosis in breast cancer cells but not in normal cells. Significantly, the release of Dox is correlated positively with the quantities of tumor mRNA, which is according to various stages of tumor progression, and so can decrease effectively side effects of Dox.
Assuntos
Neoplasias da Mama/patologia , Portadores de Fármacos/química , Ouro/química , Espaço Intracelular/metabolismo , Nanopartículas Metálicas/química , Imagem Molecular/métodos , Sondas de Oligonucleotídeos/metabolismo , Sequência de Bases , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Preparações de Ação Retardada , Doxorrubicina/química , Doxorrubicina/metabolismo , Humanos , Sondas de Oligonucleotídeos/genética , RNA Mensageiro/metabolismoRESUMO
A bi-photosensitizer molecular beacon (bi-PS MB) is assembled by coupling two PS molecules, respectively, onto the opposite ends of a single MB. The MB can be triggered by a tumor marker-survivin mRNA. Fluorescence and cytotoxic (1)O(2) generation occur effectively in breast cancer cells, but not in normal cells. Compared with a single-PS MB, a bi-PS MB exhibits much-enhanced properties in the signal-to-background ratio and (1)O(2) generation simultaneously.