Disease relevance of MAG

• By RNase protection assay, MAG mRNA was expressed in the HepG2 liver tumor cell line and in an ovarian carcinoma but not in normal liver [1].
• Rapid amplification of cDNA ends PCR yielded a 536-bp MAG fragment in HCC, macroregenerative liver nodules with dysplasia, and liver cirrhosis but not in normal liver or placenta [1].
• We have identified a novel human malignancy-associated gene (MAG) expressed in various malignant tumors including glioblastomas and hepatocellular carcinomas (HCCs) and in tumor preexisting conditions such as hepatitis C virus- and hepatitis B virus-induced liver cirrhosis [1].
• RECENT FINDINGS: Different electrophysiological parameters have been demonstrated to distinguish the anti-MAG-associated polyneuropathy from chronic inflammatory demyelinating polyneuropathy [2].
• Analyses of pathology in nerve tissue from anti-MAG patients using classical nerve biopsy or skin biopsy tissue demonstrated immunoglobulin M deposits at the site of MAG localization, demyelination and axonal degeneration [2].

High impact information on MAG

• These studies support a long-standing hypothesis regarding pathogenesis of malignancy-associated hypercalcemia [3].
• These properties are consistent with a role for PTH-like proteins as mediators of the syndrome of malignancy-associated hypercalcemia [4].
• However, the malignancy-associated increase in u-PA seems not to be affected by the plasminogen activator inhibitors [5].
• Furthermore, the clinical, mucin histochemical, and immunohistochemical findings of the metachronous adenomas show less malignancy-associated features than those of the index adenomas [6].
• Thus, the late onset of overt tumours suggests that secondary tumorigenic mutations are necessary for malignancy associated with MLL-AF9 gene fusion and that myeloproliferation provides the pool of cells in which such events can occur [7].

Chemical compound and disease context of MAG

• Thirty-two patients with a peripheral neuropathy and paraproteinemia were tested for IgM antibodies against myelin-associated protein (MAG) and sulfatide by means of enzyme-linked immunosorbent assay [8].
• Standard therapy in the United States for malignancy-associated hyperuricemia consists of hydration, alkalinization, and allopurinol [9].
• Treatment of malignancy-associated hypercalcemia with intravenous aminohydroxypropylidene diphosphonate [10].
• The current report describes the purification to homogeneity from a humoral hypercalcemia of malignancy-associated tumor of a novel, basic, highly potent PTH-like adenylate cyclase-stimulating protein [11].
• Intravenously administered clodronate appears to be an excellent agent for the acute treatment of malignancy-associated hypercalcemia [12].

Biological context of MAG

• The subtle CNS phenotype resulting from genetic ablation of MAG expression has made mechanistic analysis of its functional role in these difficult [13].
• Atypical Notch ligands transduce signals to the CSL-NICD-Deltex complex for the differentiation of progenitor cells through MAG transcriptional activation [14].
• To define a serologic response to HPV, we synthesized peptides based on sequences deduced from the genome of HPV type 16, the most common malignancy-associated type of HPV [15].
• The results indicate that screening for infection with malignancy-associated types of HPV may be possible by simple synthetic peptide-based serology [15].
• Acquired immunodeficiency syndrome indicates opportunistic infection or unusual malignancy associated with a marked deficiency of cell mediated immunity in the absence of any other cause of the immune defect [16].

Anatomical context of MAG

• SUMMARY: Therapy in patients with anti-MAG neuropathy is directed at reducing the antibody concentration, blocking the effector mechanisms and depleting the monoclonal B cells [2].
• Following central nervous system injury, axons regenerate poorly, in part due to the presence of molecules associated with myelin that inhibit axonal outgrowth, including myelin-associated glycoprotein (MAG) [17].
• At 72 h post-injury, increased immunoreactivity for MAG was seen in the ipsilateral cortex, thalamus and hippocampus of brain-injured animals, and anti-MAG mAb was detectable in the hippocampus, fimbria and ventricles [17].
• Clustering of gangliosides in the absence of inhibitors such as MAG is also shown to inhibit neurite outgrowth in culture [18].
• The myelin-associated glycoprotein (MAG) is a type I membrane-spanning protein expressed exclusively in oligodendrocytes and Schwann cells [13].

Associations of MAG with chemical compounds

• MAG is a Schwann cell-based glycoprotein and has been implicated as a mediator of an outside-in signaling cascade influencing the cytoskeletal integrity of axons [2].
• Synthesis of Neu5Ac oligosaccharides and analogues by transglycosylation and their binding properties as ligands to MAG [19].
• Our aim was to study the relation between serum 1,25-dihydroxyvitamin D and humoral activity in malignancy-associated hypercalcaemia [20].
• The mechanism for glucose hypermetabolic activity of PXA is not clear; however, the positive findings obtained from FDG-PET may not always indicate the degree of malignancy associated with PXA [21].
• Efficacy of aminohydroxypropylidene diphosphonate in the treatment of malignancy-associated hypercalcaemia [22].

Regulatory relationships of MAG

• PTHrP analogues which strongly inhibit PTHrP AC-stimulation showed promise for the treatment of malignancy-associated hypercalcemia in animal trials but failed in human ones [23].
• Parathyroid hormone is suppressed in malignancy-associated hypercalcemia and elevated in primary hyperparathyroidism [24].

Other interactions of MAG

• Effects of treatment of malignancy-associated hypercalcemia on serum parathyroid hormone-related protein [25].
• Parathyroid hormone-related protein (PTHrP) is the primary mediator of hypercalcemia in patients with malignancy-associated hypercalcemia [25].
• Familial hyperparathyroid syndromes involving mutations of HRPT2 (also CDC73), a tumor suppressor, are important to identify because the relatively high incidence of parathyroid malignancy associated with such mutations warrants a specific surveillance strategy [26].
• p53 and FHIT mutations and microsatellite alterations in malignancy-associated pleural effusion [27].
• These results are significant because they show that HA-ESX is able to differentially activate several malignancy-associated gene promoters, and that ESX expression is required for cellular survival of nontransformed MCF-12A and transformed T47D human mammary cells [28].

Analytical, diagnostic and therapeutic context of MAG

• By RT-PCR, MAG expression was not found in 12 different normal tissues but found in 46 of 51 (90%) premalignant and malignant tissues of various sites [1].
• The expression of MAG was characterized using reverse transcription-PCR (RT-PCR), rapid amplification of cDNA ends PCR, RNA dot blotting, RNase protection assay, and Northern blot analysis [1].
• One group of these rats (n = 14 sham, n = 11 injured) was killed at 72 h post-injury for verification of drug diffusion and MAG immunohistochemistry [17].
• A retrospective study of patients with ARM and associated urogenital abnormalities admitted in the department of paediatric surgery of Sylhet MAG Osmani Medical College Hospital between 1998 and 2002 was undertaken [29].
• Three allografts were subsequently lost in the MAG group [30].

References