The Experts below are selected from a list of 1297980 Experts worldwide ranked by ideXlab platform
Tianmin Cheng - One of the best experts on this subject based on the ideXlab platform.
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β2 microglobulin emerging as a promising cancer therapeutic target
Drug Discovery Today, 2009Co-Authors: Chunmeng Shi, Ying Zhu, Leland W K Chung, Tianmin ChengAbstract:Beta2-Microglobulin, a MHC class I subunit, is found to act similarly to a prototypical oncogenic factor capable of stimulating growth and progression of various cancers and plays a key regulatory role in stimulating cancer bone metastasis. Free beta2M in serum or urine has been regarded as an independent biomarker in several cancers. Specific antibodies to beta2M have remarkable tumoricidal activity for both solid tumors and blood malignancies and are shown to be selective to tumor cells, but caused no toxicity in normal cells. These surprising data strongly suggest that beta2M is a promising new therapeutic target for human cancers.
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Beta2-Microglobulin: emerging as a promising cancer therapeutic target.
Drug discovery today, 2008Co-Authors: Chunmeng Shi, Ying Zhu, Leland W K Chung, Tianmin ChengAbstract:Beta2-Microglobulin, a MHC class I subunit, is found to act similarly to a prototypical oncogenic factor capable of stimulating growth and progression of various cancers and plays a key regulatory role in stimulating cancer bone metastasis. Free beta2M in serum or urine has been regarded as an independent biomarker in several cancers. Specific antibodies to beta2M have remarkable tumoricidal activity for both solid tumors and blood malignancies and are shown to be selective to tumor cells, but caused no toxicity in normal cells. These surprising data strongly suggest that beta2M is a promising new therapeutic target for human cancers.
Giampaolo Merlini - One of the best experts on this subject based on the ideXlab platform.
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Beta2-Microglobulin causes abnormal phosphatidylserine exposure in human red blood cells
Molecular bioSystems, 2010Co-Authors: Barbara Pavone, Giampaolo Merlini, Sonia Bucci, Vittorio Sirolli, Piero Del Boccio, Marianna Di Rienzo, P. Felaco, Luigi Amoroso, Paolo Sacchetta, Carmine Di IlioAbstract:The exposure of the aminophospholipid phosphatidylserine on the external leaflet of red blood cell plasma membrane can have several pathophysiological consequences with particular regard to the processes of cell phagocytosis, haemostasis and cell-cell interaction. A significant increase in phosphatidylserine-exposing erythrocytes has been reported in chronic haemodialysis patients and found to be strongly influenced by the uraemic milieu. To identify uraemic compound(s) enhancing phosphatidylserine externalization in erythrocytes, we fractionated by chromatographic methods the ultrafiltrate obtained during dialysis, and examined by flow cytometry the effect of the resulting fractions on phosphatidylserine exposure in human red cells. Chromatographic procedures disclosed a homogeneous fraction able to increase erythrocyte phosphatidylserine exposure. The inducer of such externalization was identified by monodimensional gel electrophoresis and mass spectrometry investigations as Beta2-Microglobulin. To confirm the Beta2-Microglobulin effect and to examine the influence of protein glycation (as it occurs in uraemia) on phosphatidylserine erythrocyte exposure, erythrocytes from normal subjects were incubated with recombinant Beta2-Microglobulin (showing no glycation sites at mass analysis), commercial Beta2-Microglobulin (8 glycation sites), or with in vitro glycated recombinant Beta2-Microglobulin (showing multiple glycation sites). Elevated concentrations of Beta2-Microglobulin (corresponding to plasma levels reached in dialysis patients) increased slightly but significantly the protein's ability to externalize phosphatidylserine on human erythrocytes. Such an effect was markedly enhanced by glycated forms of the protein. Beta2-Microglobulin is recognized as a surrogate marker of middle-molecule uraemic toxins and represents a key component of dialysis-associated amyloidosis. Our study adds further evidence to the potential pathophysiologic consequences of Beta2-Microglobulin accumulation in chronic uraemic patients.
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Proteomics of β2-microglobulin amyloid fibrils
Biochimica et biophysica acta, 2005Co-Authors: Monica Stoppini, Palma Mangione, Maria Chiara Monti, Sofia Giorgetti, Loredana Marchese, Patrizia Arcidiaco, Laura Verga, S. Segagni, Piero Pucci, Giampaolo MerliniAbstract:Knowledge on the chemical structure of Beta2-Microglobulin in natural amyloid fibrils is quite limited because of the difficulty in obtaining tissue samples suitable for biochemical studies. We have reviewed the available information on the chemical modifications and we present new data of Beta2-Microglobulin extracted from non-osteotendinous tissues. Beta2-Microglobulin can accumulate in these compartments after long-term haemodialysis but rarely forms amyloid deposits. We confirm that truncation at the N-terminus is an event specific to Beta2-Microglobulin derived from fibrils but is not observed in the Beta2-Microglobulin from plasma or from the insoluble non-fibrillar material deposited in the heart and spleen. We also confirm the partial deamidation of Asn 17 and Asn 42, as well as the oxidation of Met 99 in fibrillar Beta2-Microglobulin. Other previously reported chemical modifications cannot be excluded, but should involve less than 1-2% of the intact molecule.
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Use of anti-(beta2 microglobulin) mAb to study formation of amyloid fibrils.
European journal of biochemistry, 1997Co-Authors: Monica Stoppini, Palma Mangione, Giampaolo Merlini, Vittorio Bellotti, Giuseppina FerriAbstract:Three mAbs, IgG1k 1F11, 7B6 and 14H3, were raised against in vitro-self-aggregated Beta2-Microglobulin. They recognize the native and unfolded forms of the protein and bind its fibrillar form that is present in amyloid tissue. When assayed in fibrillogenesis tests in vitro, mAb 14H3 inhibited fibril formation from Beta2-Microglobulin. This mAb recognizes a sequential epitope corresponding to the C-terminal octapeptide, residues 92-99, of Beta2-Microglobulin. By using synthetic peptides it has been found that the integrity of the sequence is essential for the formation of the immunocomplex: the binding affinity is lowered by one order of magnitude (Kd from 10(-7) M to 10(-6) M) by removal of Met99 and completely abolished when both Asp98 and Met99 are lost or Arg98 is substituted with Lys. The other two mAbs, 1F11 and 7B6, which bind sequences 20-41 and 63-75, respectively, are without effect on Beta2-Microglobulin fibrillogenesis. These two mAbs recognize Beta2-Microglobulin bound to the heavy chain in the major histocompatibility complex of type I located in the cell membrane, a property which is not shared by mAb 14H3.
Leland W K Chung - One of the best experts on this subject based on the ideXlab platform.
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β2 microglobulin emerging as a promising cancer therapeutic target
Drug Discovery Today, 2009Co-Authors: Chunmeng Shi, Ying Zhu, Leland W K Chung, Tianmin ChengAbstract:Beta2-Microglobulin, a MHC class I subunit, is found to act similarly to a prototypical oncogenic factor capable of stimulating growth and progression of various cancers and plays a key regulatory role in stimulating cancer bone metastasis. Free beta2M in serum or urine has been regarded as an independent biomarker in several cancers. Specific antibodies to beta2M have remarkable tumoricidal activity for both solid tumors and blood malignancies and are shown to be selective to tumor cells, but caused no toxicity in normal cells. These surprising data strongly suggest that beta2M is a promising new therapeutic target for human cancers.
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Beta2-Microglobulin: emerging as a promising cancer therapeutic target.
Drug discovery today, 2008Co-Authors: Chunmeng Shi, Ying Zhu, Leland W K Chung, Tianmin ChengAbstract:Beta2-Microglobulin, a MHC class I subunit, is found to act similarly to a prototypical oncogenic factor capable of stimulating growth and progression of various cancers and plays a key regulatory role in stimulating cancer bone metastasis. Free beta2M in serum or urine has been regarded as an independent biomarker in several cancers. Specific antibodies to beta2M have remarkable tumoricidal activity for both solid tumors and blood malignancies and are shown to be selective to tumor cells, but caused no toxicity in normal cells. These surprising data strongly suggest that beta2M is a promising new therapeutic target for human cancers.
Chunmeng Shi - One of the best experts on this subject based on the ideXlab platform.
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β2 microglobulin emerging as a promising cancer therapeutic target
Drug Discovery Today, 2009Co-Authors: Chunmeng Shi, Ying Zhu, Leland W K Chung, Tianmin ChengAbstract:Beta2-Microglobulin, a MHC class I subunit, is found to act similarly to a prototypical oncogenic factor capable of stimulating growth and progression of various cancers and plays a key regulatory role in stimulating cancer bone metastasis. Free beta2M in serum or urine has been regarded as an independent biomarker in several cancers. Specific antibodies to beta2M have remarkable tumoricidal activity for both solid tumors and blood malignancies and are shown to be selective to tumor cells, but caused no toxicity in normal cells. These surprising data strongly suggest that beta2M is a promising new therapeutic target for human cancers.
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Beta2-Microglobulin: emerging as a promising cancer therapeutic target.
Drug discovery today, 2008Co-Authors: Chunmeng Shi, Ying Zhu, Leland W K Chung, Tianmin ChengAbstract:Beta2-Microglobulin, a MHC class I subunit, is found to act similarly to a prototypical oncogenic factor capable of stimulating growth and progression of various cancers and plays a key regulatory role in stimulating cancer bone metastasis. Free beta2M in serum or urine has been regarded as an independent biomarker in several cancers. Specific antibodies to beta2M have remarkable tumoricidal activity for both solid tumors and blood malignancies and are shown to be selective to tumor cells, but caused no toxicity in normal cells. These surprising data strongly suggest that beta2M is a promising new therapeutic target for human cancers.
Palma Mangione - One of the best experts on this subject based on the ideXlab platform.
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Proteomics of β2-microglobulin amyloid fibrils
Biochimica et biophysica acta, 2005Co-Authors: Monica Stoppini, Palma Mangione, Maria Chiara Monti, Sofia Giorgetti, Loredana Marchese, Patrizia Arcidiaco, Laura Verga, S. Segagni, Piero Pucci, Giampaolo MerliniAbstract:Knowledge on the chemical structure of Beta2-Microglobulin in natural amyloid fibrils is quite limited because of the difficulty in obtaining tissue samples suitable for biochemical studies. We have reviewed the available information on the chemical modifications and we present new data of Beta2-Microglobulin extracted from non-osteotendinous tissues. Beta2-Microglobulin can accumulate in these compartments after long-term haemodialysis but rarely forms amyloid deposits. We confirm that truncation at the N-terminus is an event specific to Beta2-Microglobulin derived from fibrils but is not observed in the Beta2-Microglobulin from plasma or from the insoluble non-fibrillar material deposited in the heart and spleen. We also confirm the partial deamidation of Asn 17 and Asn 42, as well as the oxidation of Met 99 in fibrillar Beta2-Microglobulin. Other previously reported chemical modifications cannot be excluded, but should involve less than 1-2% of the intact molecule.
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Preliminary crystallographic characterization of the human beta2 microglobulin His31Tyr mutant in a tetrameric assembly.
Acta crystallographica. Section D Biological crystallography, 2003Co-Authors: Simone Zuccotti, Palma Mangione, Vittorio Bellotti, Camillo Rosano, Martino BolognesiAbstract:Patients receiving prolonged haemodialysis treatment are exposed to a variety of arthropathies and bone lesions arising from deposition of amyloid material in the skeletal system. beta2 microglobulin is the 11.7 kDa light chain of the class I major histocompatibility complex, from which it is normally released to plasmatic fluids, transported to kidneys and excreted. Owing to renal failure it accumulates, giving rise to dialysis-related amyloidosis, a severe disease found in patients receiving dialysis for several years. The three-dimensional structure of beta2 microglobulin is known to be based on a seven-stranded beta-sandwich fold, typical of the class C immunoglobulin superfamily. Analysis of the protein fold in different mutants and/or crystal environments and of its structural stability may help in understanding the molecular bases of amyloid fibril formation and of diseases related to protein misfolding. Here, the preliminary crystallographic analysis of the His31Tyr beta2 microglobulin mutant, designed to abolish the copper-ion binding observed in the wild-type protein, is presented. The protein mutant displays increased fold stability, faster folding kinetics and crystallizes in the tetragonal C222(1) space group, with unit-cell parameters a = 105.2, b = 150.2, c = 93.7 A and four molecules per asymmetric unit.
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Beta2-Microglobulin can be refolded into a native state from ex vivo amyloid fibrils.
European journal of biochemistry, 1998Co-Authors: Vittorio Bellotti, Monica Stoppini, Palma Mangione, Margaret Sunde, Carol V. Robinson, Lia Asti, Diego Brancaccio, Giuseppina FerriAbstract:Beta2-Microglobulin fibrils have been extracted from the femoral head of a patient who has been under chronic haemodialysis for 11 years. The primary structure of the N-terminal portion of the protein and mass determination by electrospray mass spectrometry demonstrate that Beta2-Microglobulin, extracted as fibrils by the water extraction procedure, was not glycated and that Asn17 was not deamidated. Limited proteolysis was observed in more than 20% of Beta2-Microglobulin molecules and the main cleavage sites were at the C-terminus of Lys6 and Tyr10. Beta2-Microglobulin from fibrils has been purified by gel filtration in 6 M Gdn/HCl and submitted to a refolding procedure. The refolding conditions have been determined through the study of the unfolding pathway of the native protein. Beta2-Microglobulin is stable at neutral pH where it displays a lower tendency to self-aggregate than in acidic conditions. Pulse dilution and extensive dialysis in refolding buffer at pH 7.5 yields Beta2-Microglobulin with a tertiary structure identical to that of the native form. The CD spectrum in the near-ultraviolet region and the spectrum of the intrinsic fluorescence of Trp overlap those of the native protein, but the CD spectrum in the far-ultraviolet region is affected by the contribution of oligomers created by Beta2-Microglobulin fragments that reduce the positive light polarisation at 205 nm typical of native Beta2-Microglobulin.
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Use of anti-(beta2 microglobulin) mAb to study formation of amyloid fibrils.
European journal of biochemistry, 1997Co-Authors: Monica Stoppini, Palma Mangione, Giampaolo Merlini, Vittorio Bellotti, Giuseppina FerriAbstract:Three mAbs, IgG1k 1F11, 7B6 and 14H3, were raised against in vitro-self-aggregated Beta2-Microglobulin. They recognize the native and unfolded forms of the protein and bind its fibrillar form that is present in amyloid tissue. When assayed in fibrillogenesis tests in vitro, mAb 14H3 inhibited fibril formation from Beta2-Microglobulin. This mAb recognizes a sequential epitope corresponding to the C-terminal octapeptide, residues 92-99, of Beta2-Microglobulin. By using synthetic peptides it has been found that the integrity of the sequence is essential for the formation of the immunocomplex: the binding affinity is lowered by one order of magnitude (Kd from 10(-7) M to 10(-6) M) by removal of Met99 and completely abolished when both Asp98 and Met99 are lost or Arg98 is substituted with Lys. The other two mAbs, 1F11 and 7B6, which bind sequences 20-41 and 63-75, respectively, are without effect on Beta2-Microglobulin fibrillogenesis. These two mAbs recognize Beta2-Microglobulin bound to the heavy chain in the major histocompatibility complex of type I located in the cell membrane, a property which is not shared by mAb 14H3.