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#26486787   2015/10/20 To Up

Identification of the Ki-1 antigen (CD30) as a novel therapeutic target in systemic mastocytosis.

The Ki-1 antigen (CD30) is an established therapeutic target in patients with Hodgkin lymphoma and anaplastic large-cell lymphoma. We have recently shown that CD30 is expressed abundantly in the cytoplasm of neoplastic mast cells (MCs) in patients with advanced systemic mastocytosis (SM). In the current study, we asked whether CD30 is expressed on the surface of neoplastic MCs in advanced SM, and whether this surface structure may serve as therapeutic target in SM. As assessed by flow cytometry, CD30 was found to be expressed on the surface of neoplastic MCs in 3 of 25 patients (12%) with indolent SM, 4 of 7 patients (57%) with aggressive SM, and 4 of 7 patients (57%) with MC leukemia. The immature RAS-transformed human MC line MCPV-1.1 also expressed cell surface CD30, whereas the KIT-transformed MC line HMC-1.2 expressed no detectable CD30. The CD30-targeting antibody-conjugate brentuximab-vedotin inhibited proliferation in neoplastic MCs, with lower IC50 values obtained in CD30(+) MCPV-1.1 cells (10 µg/mL) compared with CD30(-) HMC-1.2 cells (>50 µg/mL). In addition, brentuximab-vedotin suppressed the engraftment of MCPV-1.1 cells in NSG mice. Moreover, brentuximab-vedotin produced apoptosis in all CD30(+) MC lines tested as well as in primary neoplastic MCs in patients with CD30(+) SM, but did not induce apoptosis in neoplastic MCs in patients with CD30(-) SM. Furthermore, brentuximab-vedotin was found to downregulate anti-IgE-induced histamine release in CD30(+) MCs. Finally, brentuximab-vedotin and the KIT D816V-targeting drug PKC412 produced synergistic growth-inhibitory effects in MCPV-1.1 cells. Together, CD30 is a promising new drug target for patients with CD30(+) advanced SM.
Katharina Blatt, Sabine Cerny-Reiterer, Juliana Schwaab, Karl Sotlar, Gregor Eisenwort, Gabriele Stefanzl, Gregor Hoermann, Matthias Mayerhofer, Mathias Schneeweiss, Sylvia Knapp, Thomas Rülicke, Emir Hadzijusufovic, Karin Bauer, Dubravka Smiljkovic, Michael Willmann, Andreas Reiter, Hans-Peter Horny, Peter Valent

1831 related Products with: Identification of the Ki-1 antigen (CD30) as a novel therapeutic target in systemic mastocytosis.

0.1ml (1mg/ml)1mg0.1ml0.1ml (1mg/ml)0.1ml0.1ml0.1ml (1mg/ml)0.1ml50ul (1mg/ml)0.1ml

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#3318239   // To Up

[Use of solid-phase immunoenzyme analysis for determining allergen-specific IgE antibodies].

An ELISA system for the detection of allergen-specific IgE antibodies to ragweed allergen has been developed. The system is highly sensitive and specific. Ragweed pollen allergen has been obtained by the dialysis of water-soluble extract through a kidney membrane. The high molecular fraction of ragweed allergen, showing the whole of the allergenic activity detected by skin tests in untreated patients, has been used for coating polystyrene assay plates. To detect IgE antibodies to ragweed allergen, the conjugate of sheep anti-IgE antibodies with horse-radish peroxidase has been used. The level of allergen-specific IgE antibodies has been determined on the basis of the data on the optical density of the samples in comparison with that of the normal sera. The correlation factor of the results obtained in the assay of specific IgE antibodies with the newly developed assay system and with the commercial kit Phadezyme RAST manufactured by Pharmacia AB (Sweden) has proved to be 0.82 at n = 39, p less than 0.01, while the variation factor in the reproduction of the assay results has proved to be 12% at n = 40.
V B Gervazieva, I G Ovsiannikova, N I Voronkin, N N Sorochinskaia, B N Raĭkis

1213 related Products with: [Use of solid-phase immunoenzyme analysis for determining allergen-specific IgE antibodies].

100.00 ug4 Membranes/Box2 Pieces/Box4 Membranes/Box2 Pieces/Box4 Arrays/Slide2 Pieces/Box4 Membranes/Box2 Pieces/Box4 Membranes/Box4 Arrays/Slide

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