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1.
J Invest Dermatol ; 131(5): 1129-38, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21326296

RESUMO

Frequent somatic mutations of BRAF (v-raf murine sarcoma viral oncogene homolog B) exon T1799A, which are implicated in the initial events of promutagenic cellular proliferation, are detected in both malignant melanomas (MM) and melanocytic nevi (MN). Most of the data regarding BRAF exon T1799A mutation have been from Caucasian cohorts, and a comprehensive screening of a homogeneous population is lacking. A total of 379 cases of MN and 195 cases of MM were collected from Chinese Han living in three geographical regions in China, i.e., northeast, southwest, and northwest China. BRAF exon T1799A mutation was detected by PCR and sequencing from microdissected tumors. In all, 59.8% cases of MN harbored BRAF exon T1799A mutation. Samples from regions with high UV exposure had higher detection rates than regions with lower UV exposure (73.5, 67.0, and 38.9%, respectively; χ(2) = 31.674, P = 1.59E-7). There were no differences in mutation rates between congenital and acquired MN; however, acquired MN with advanced age of onset had a higher mutation rate than those with younger age of onset (χ(2) = 13.23, P = 0.02). In all, 15.0% cases of MM harbored the BRAF mutation. The mutation rate in MM was not affected by region, histological type, gender, pattern of UV exposure, and age. The study suggests that the mutation is not necessarily associated with malignant transformation.


Assuntos
Éxons/genética , Melanoma/genética , Mutação/genética , Nevo Pigmentado/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Adolescente , Adulto , Povo Asiático/genética , Povo Asiático/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Melanoma/epidemiologia , Nevo Pigmentado/epidemiologia , Prevalência , Estudos Retrospectivos , Neoplasias Cutâneas/epidemiologia , Raios Ultravioleta/efeitos adversos , Adulto Jovem
2.
Inflamm Res ; 59(10): 879-87, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20490892

RESUMO

OBJECTIVE: We evaluated different dose effects of rIL-25 on acute ulcerative colitis. MATERIALS AND METHODS: Mice were fed 2.5% dextran sulfate sodium (DSS) for 5 days while infused i.p. with repeated doses of rIL-25 (0.2, 0.4 and 0.8 microg) in PBS or PBS only after every 24 h at the same time as the start of the DSS exposure. Clinical, macroscopical and microscopical assessment of colitis severity with survival study was performed. Colonic IL-25 expression and production of IFN-gamma, IL-10 and IL-4 was also analyzed. RESULTS: At a dose of 0.2 microg, colitis was aggravated with high mortality, better improvements were observed at a dose of 0.4 microg, and colitis-induced diarrhea was reversed at a dose of 0.8 microg. The expression of IL-25 was found to decrease in severe colitis. Moreover, IL-25 inhibited production of mucosal IFN-gamma, induced increase in IL-10 but not IL-4. CONCLUSION: Improvements in DSS-induced colitis in response to IL-25 suggest IL-25's protective role by mechanisms including inhibition of IFN-gamma with enhancement of anti-inflammatory release.


Assuntos
Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana/farmacologia , Interleucinas/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Animais , Colite/imunologia , Colite/patologia , Colo/citologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Relação Dose-Resposta a Droga , Feminino , Interferon gama/imunologia , Interleucina-10/imunologia , Interleucina-4/imunologia , Interleucinas/genética , Interleucinas/imunologia , Interleucinas/farmacologia , Estimativa de Kaplan-Meier , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/farmacologia
3.
Vaccine ; 28(18): 3134-42, 2010 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-20197133

RESUMO

Tuberculosis is one of the leading causes of mortality from an infectious disease worldwide, however, the efficacy of BCG vaccine against adult pulmonary tuberculosis still remains instability. Therefore, it is an urgent work to develop both safe and effective vaccine to TB. To clarify the liposome encapsulated DNA vaccine was effectively working as a vaccine delivery system to evoke mucosal intestinal immune responses. A Mycobacterium pcDNA3.1(+)/Ag85A DNA was constructed and encapsulated into liposome. Ag85A protein antigen was observed to substantially express in the epithelium, microfold cells (M cells), dendritic cells (DCs) and Peyer's patches (pp) of the small intestine, respectively, after oral administration into C57BL/6 mice 3 times each 14 days interval. Furthermore, levels of IL-2 and IFN-gamma in the IELs isolated from the small intestine were markedly increased, IL-4 level was not significantly changed as compared to those in control group after oral administration of Ag85A DNA encapsulated in liposome, together with the augmented Ag85A-specific cytotoxicity of IELs, indicating a local Th1 dominant cellular immune response was elicited, and thus enhanced cytotoxicity of IELs as compared to those in control mice. Furthermore, sIgA level was also elevated in liposomal encapsulated Ag85A DNA immunized mice. These data indicated that oral vaccination with the liposomal-pcDNA 3.1(+)/Ag85A DNA is able to induce antigen specific mucosal cellular and humoral immune responses. Especially, cellular compartment in the epithelium of small intestine plays a key role on the regulation of immune response to eliminate TB. These findings have important understanding and possible implications for the design of new strategies based on oral DNA vaccine on regulation of immune response in protection against TB. Further study is clearly necessary to improve the effectiveness of Ag85A DNA vaccines against TB as compared with BCG.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Lipossomos/administração & dosagem , Vacinas contra a Tuberculose/administração & dosagem , Vacinas contra a Tuberculose/imunologia , Vacinas de DNA/administração & dosagem , Vacinas de DNA/imunologia , Aciltransferases/genética , Aciltransferases/imunologia , Administração Oral , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Feminino , Imunoglobulina A Secretora/sangue , Interferon gama/metabolismo , Interleucina-2/metabolismo , Leucócitos Mononucleares/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Células Th1/imunologia
4.
Cell Mol Immunol ; 5(6): 425-31, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19118508

RESUMO

The role of interleukin 25 (IL-25) in a number of human diseases still has not been extensively studied, here we attempt to evaluate the role of recombinant IL-25 (rIL-25) in the development of dextran sulfate sodium (DSS)-induced experimental colitis. Acute colitis was induced in female C57BL/6 mice by oral administration of 2.5% DSS in drinking water ad libitum. At the same time as the start of DSS exposure, mice were injected intraperitoneally with 0.4 microg of rIL-25 or PBS. Then disease activity index (DAI), histological changes and survival rate were observed. The levels of IL-17, IL-23, and TGF-beta1 in colon tissues were determined by ELISA, and the production of IL-17 by CD4(+)/CD8(+) T cells was detected by intracellular flow cytometry. In contrast to the DSS treated mice, DSS + rIL-25 treated mice displayed a lower DAI, limited histological changes and prolonged survival. The levels of IL-23 and TGF-beta1 were significantly elevated in the DSS + rIL-25 treated mice compared to the DSS treated mice. There was no significant difference in the production of IL-17 in colon tissues and CD4(+)/CD8(+) T cells between the DSS + rIL-25 treated mice and DSS treated mice. Our findings suggest the role of IL-25 in inhibiting development and progression of acute colitis in DSS-induced mouse colitis model.


Assuntos
Colite/tratamento farmacológico , Colite/patologia , Interleucina-17/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Sulfato de Dextrana , Progressão da Doença , Feminino , Citometria de Fluxo , Interleucina-17/metabolismo , Interleucina-17/farmacologia , Interleucina-23/metabolismo , Estimativa de Kaplan-Meier , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/farmacologia , Fator de Crescimento Transformador beta1/metabolismo
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