Human Immunoglobulin G (human + immunoglobulin_g)

Distribution by Scientific Domains

Selected Abstracts

Vorinostat enhances the antimyeloma effects of melphalan and bortezomib

Richard A. Campbell
Abstract Objectives:, Examine the antitumor activity of the histone deacetylase inhibitor vorinostat's antitumor activity against multiple myeloma (MM) using cell lines and a murine xenograft model. Methods:, RPMI8226, U266, and MM1S cells were cultured for 48 h in the presence of media, vorinostat, melphalan, or bortezomib alone, or combinations of vorinostat with melphalan or bortezomib. Cell proliferation was measured using the MTS [3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfphophenyl)-2H-tetrazolium, inner salt] assay. Severe combined immunodeficient mice bearing LAG,-1B tumors were treated with vorinostat [30, 60, or 100 mg/kg daily for five consecutive days per week (qd×5d), 100 or 300 mg/kg daily for 2 d/wk (qd×2d)], melphalan (1, 3, or 10 mg/kg qd×1d), bortezomib (0.25 or 0.5 mg/kg qd×2d), or combinations thereof for 35 d. Tumor growth was determined via measurement of human immunoglobulin G (hIgG) levels and tumor volume. Results and Conclusions:, Vorinostat enhanced the anti-MM effects of melphalan and bortezomib in vitro. Synergism was observed with vorinostat and melphalan in RPMI8226 and U266 cell lines. Vorinostat 100 mg/kg in combination with melphalan 3 mg/kg resulted in significant inhibition of tumor growth in vivo, compared with control (tumor volume P = 0.0001; hIgG P = 0.0001), single-agent vorinostat (tumor volume P = 0.0025; hIgG P = 0.0137), and single-agent melphalan (tumor volume P = 0.0043; hIgG P = 0.0426). Vorinostat also enhanced the antimyeloma effects of bortezomib in vivo. Vorinostat enhances the anti-MM activity of melphalan and bortezomib in vitro and in vivo. This study provides rationale for further evaluation of vorinostat in combination with chemotherapeutic agents and bortezomib for the treatment of MM. [source]

Binding site on human immunoglobulin G for the affinity ligand HWRGWV

Haiou Yang
Abstract Affinity ligand HWRGWV has demonstrated the ability to isolate human immunoglobulin G (hIgG) from mammalian cell culture media. The ligand specifically binds hIgG through its Fc portion. This work shows that deglycosylation of hIgG has no influence on its binding to the HWRGWV ligand and the ligand does not compete with Protein A or Protein G in binding hIgG. It is suggested by the mass spectrometry (MS) data and docking simulation that HWRGWV binds to the pFc portion of hIgG and interacts with the amino acids in the loop Ser383,Asn389 (SNGQPEN) located in the CH3 domain. Subsequent modeling has suggested a possible three-dimensional minimized solution structure for the interaction of hIgG and the HWRGWV ligand. The results support the fact that a peptide as small as a hexamer can have specific interactions with large proteins such as hIgG. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Microchannels created by sugar and metal microneedles: Characterization by microscopy, macromolecular flux and other techniques

Guohua Li
Abstract The objective of this study was to investigate the feasibility of using microneedle technology to enhance transcutaneous permeation of human immunoglobulin G (IgG) across hairless rat skin. Microchannels created by maltose and metal (DermaRollerÔ) microneedles were characterized by techniques such as methylene blue staining, histological examination, and calcein imaging. Methylene blue staining and histological sections of treated skin showed that maltose microneedles and DermaRollerÔ breached the skin barrier by creating microchannels in the skin with an average depth of ,150,µm, as imaged by confocal microscopy. Calcein imaging and pore permeability index values suggested the uniformity of the created pores in microneedle-treated skin. Transdermal studies with IgG indicated a flux rate of 45.96,ng/cm2/h, in vitro, and a Cmax of 7.27,ng/mL, in vivo, for maltose microneedles-treated skin while a flux rate of 353.17,ng/cm2/h, in vitro, and a Cmax of 9.33,ng/mL, in vivo, was achieved for DermaRollerÔ-treated skin. Transepidermal water loss measurements and methylene blue staining, in vivo, indicated the presence of microchannels for upto 24,h, when occluded. In conclusion, the microchannels created by maltose microneedles and DermaRollerÔ resulted in the percutaneous enhancement of a macromolecule, human IgG. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1931,1941, 2010 [source]

Reversal of immune thrombocytopenia in mice by cross-linking human immunoglobulin G with a high-affinity monoclonal antibody

Renée Bazin
Summary Intravenous immunoglobulins (IVIgs) are used to treat an increasing number of autoimmune diseases, but their exact mechanism of action remains unknown. This study showed that cross-linking of human IgG present in IVIg preparations using a mouse monoclonal anti-human IgG generated complexes that prevented or reversed thrombocytopenia in mice more efficiently than IVIg. Furthermore, biologically active complexes were obtained simply by adding the monoclonal antibody to human serum. These results suggest the possible development of an IVIg-free substitute through the ex vivo, and possibly in vivo, formation of immune complexes containing autologous IgG of immune thrombocytopenic purpura patients. [source]