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1.
J Mass Spectrom ; 52(3): 165-173, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28117928

RESUMO

For identification of clinically relevant masses to predict status, grade, relapse and prognosis of colorectal cancer, we applied Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) to a tissue micro array containing formalin-fixed and paraffin-embedded tissue samples from 349 patients. Analysis of our MALDI-IMS data revealed 27 different m/z signals associated with epithelial structures. Comparison of these signals showed significant association with status, grade and Ki-67 labeling index. Fifteen out of 27 IMS signals revealed a significant association with survival. For seven signals (m/z 654, 776, 788, 904, 944, 975 and 1013) the absence and for eight signals (m/z 643, 678, 836, 886, 898, 1095, 1459 and 1477) the presence were associated with decreased life expectancy, including five masses (m/z 788, 836, 904, 944 and 1013) that provided prognostic information independently from the established prognosticators pT and pN. Combination of these five masses resulted in a three-step classifier that provided prognostic information superior to univariate analysis. In addition, a total of 19 masses were associated with tumor stage, grade, metastasis and cell proliferation. Our data demonstrate the suitability of combining IMS and large-scale tissue micro arrays to simultaneously identify and validate clinically useful molecular marker. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Neoplasias Colorretais/diagnóstico , Biomarcadores Tumorais/análise , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Feminino , Formaldeído , Ensaios de Triagem em Larga Escala/métodos , Humanos , Antígeno Ki-67/análise , Masculino , Metástase Neoplásica , Inclusão em Parafina , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Análise Serial de Tecidos , Fixação de Tecidos , Carga Tumoral
2.
Prostate Cancer Prostatic Dis ; 16(2): 159-64, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23338556

RESUMO

BACKGROUND: Neuron-glia-related cell-adhesion molecule (Nr-CAM) is another potential membrane-bound target molecule for specific prostate cancer therapy. The role of Nr-CAM in normal and neoplastic prostate tissue has not been extensively studied. The aim of our study is to evaluate the prevalence of Nr-CAM expression in prostate cancer and to explore its association with phenotype and clinical disease course. METHODS: A preexisting tissue microarray including more than 3000 prostate cancers that underwent prostatectomy at our center with clinical follow-up data was used. The tissue microarray (TMA) was immunhistochemically stained for Nr-CAM. RESULTS: A total of 2883 (88.4%) of tumor samples were interpretable in our TMA analysis. Membranous Nr-CAM staining was seen in 1418 (49.2%) of 2883 analyzable cases. According to predefined criteria, staining was considered weak in 778 (27.0%), moderate in 412 (14.3%) and strong in 228 (7.9%) cancers. Significant associations were found with pathological tumor stage (P=0.0015), Gleason grade (P=0.0003), nodal stage (P=0.0061), preoperative PSA (P=0.0138) and prolonged PSA recurrence-free survival (P<0.0001). CONCLUSIONS: Nr-CAM expression is frequent in prostate cancer. High level of Nr-CAM expression is associated with favorable tumor phenotype and reduced risk of PSA recurrence. The abundant presence of Nr-CAM in prostate cancer epithelium makes Nr-CAM a potential target of therapy.


Assuntos
Moléculas de Adesão Celular/metabolismo , Calicreínas/sangue , Recidiva Local de Neoplasia/metabolismo , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/metabolismo , Idoso , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Fenótipo , Prognóstico , Prostatectomia , Neoplasias da Próstata/cirurgia , Risco , Análise Serial de Tecidos
3.
Circulation ; 105(5): 633-8, 2002 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-11827931

RESUMO

BACKGROUND: To investigate the contribution of inflammation to postangioplasty lumen loss, we used an adenoviral gene therapy approach to inhibit the central inflammatory mediator nuclear factor-kappaB (NF-kappaB) by overexpression of its natural inhibitor, IkappaBalpha. METHODS AND RESULTS: The adenovirus carrying human IkappaBalpha was applied immediately after balloon dilatation by a double-balloon catheter in a rabbit iliac artery restenosis model. Immunohistochemistry of IkappaBalpha revealed that mainly smooth muscle cells of the media but also cells of the adventitia were transduced and expressed the transgene IkappaB alpha for >/= 8 days. At this time point, intercellular adhesion molecule-1 (30%) and monocyte chemotactic protein-1 (50%) expression, as well as recruitment of macrophages into the wounded area (90%), were significantly reduced in IkappaB alpha-treated vessels. In addition, expression of inhibitor of apoptosis proteins was reduced and the percentage of apoptotic cells was increased compared with control-treated contralateral vessels. Animals killed 5 weeks after treatment exhibited a significantly reduced degree of lumen narrowing (P<0.02) on the side treated with adenovirus IkappaBalpha. The lumen gain of approximately 40% was due to positive remodeling. CONCLUSIONS: From these data, we conclude that balloon angioplasty-induced activation of NF-kappaB contributes to lumen loss likely via induction of an inflammatory response and a decrease in the rate of apoptosis. These data show for the first time that inflammation mediated by NF-kappaB is involved in postangioplasty lumen narrowing. Specific and more potent inhibitors of NF-kappaB might therefore be a useful therapeutic measure to improve clinical outcome after balloon dilatation.


Assuntos
Oclusão de Enxerto Vascular/metabolismo , Oclusão de Enxerto Vascular/prevenção & controle , Proteínas I-kappa B , NF-kappa B/metabolismo , Adenoviridae/genética , Angiografia Digital , Angioplastia com Balão/efeitos adversos , Animais , Apoptose/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CCL2/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/farmacologia , Dieta Aterogênica , Modelos Animais de Doenças , Expressão Gênica , Oclusão de Enxerto Vascular/patologia , Humanos , Artéria Ilíaca/diagnóstico por imagem , Artéria Ilíaca/metabolismo , Artéria Ilíaca/patologia , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/metabolismo , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Inibidor de NF-kappaB alfa , NF-kappa B/antagonistas & inibidores , Infiltração de Neutrófilos/efeitos dos fármacos , Coelhos , Transgenes , Grau de Desobstrução Vascular/efeitos dos fármacos
4.
Pharmazie ; 54(10): 766-7, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10563374

RESUMO

For a series of model compounds (digitonin, aescine, tomatine, stevioside and ginsenoside Rg1) it was demonstrated that neither the surface nor the interfacial tension (n-decane/water) lowering properties of saponins can be correlated with their ability to induce hemolysis. Furthermore, no correlation was observed between the surface and interfacial activities of saponins and their hemolytic properties.


Assuntos
Hemólise/efeitos dos fármacos , Saponinas/química , Saponinas/farmacologia , Algoritmos , Fenômenos Químicos , Físico-Química , Membrana Eritrocítica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Indicadores e Reagentes , Relação Estrutura-Atividade , Propriedades de Superfície , Tensão Superficial
5.
J Nat Prod ; 62(5): 670-3, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10346941

RESUMO

The oligosaccharide chain of the monodesmosidic haemolytic saponin digitonin (1) undergoes an efficient and regioselective acylation in organic solvent by use of Novozym 435 (lipase B from Candida antarctica supported on acrylic resin) in the presence of an activated ester. With vinyl acetate, acetylation occurs at C-6 OH of glucose(II) and C-4 OH of xylose to afford the previously unreported diacetyl derivative 2 and the monoacetyl derivatives 3 and 4. With vinyl laurate only the monolauryl derivative 5 is formed. The structures of these acylated digitonins have been established using modern 2D NMR techniques, which allowed complete assignments of all proton resonances. The hemolytic activity of derivatives 2-5 is significantly reduced compared to that of digitonin.


Assuntos
Digitonina/análogos & derivados , Digitonina/síntese química , Lipase , Animais , Candida/enzimologia , Sequência de Carboidratos , Bovinos , Digitonina/farmacologia , Ésteres , Hemólise , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular
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