RP215 monoclonal antibody (Mab) was initially generated against OC-3-VGH ovarian cancer cells and was shown to react with a cancer-associated carbohydrate epitope in glycoproteins designated as CA215. Additional five high affinity Mabs, designated as RCA-10, -100, -104, -110 and -111, respectively, were generated by using affinity-purified CA215 as the immunogen in this study. All RCA Mabs were found to recognize periodate-sensitive carbohydrate-associated epitope(s) and to pair with RP215 in typical sandwich enzyme immunoassays for the quantification of CA215. When compared with those of RP215, the amino acid sequence homology of the Fab regions ranged from 100% for RCA-100 to 65% for RCA-110, based on which 3 distinct Mab groups were categorized. In vitro TUNEL apoptosis and complement-dependent cytotoxicity assays were performed with these Mabs and found to have comparable inhibitory efficacy to cancer cells. Results of biochemical and immunological assays revealed that RP215, RCA-100 and RCA-10 react with the linear carbohydrate-associated epitope, whereas the others recognize the conformational form of the epitope in CA215. This study has suggested that the unique carbohydrate-associated epitope(s) is immunodominant in mice when immunized with CA215. It remains to be demonstrated if the differential anti-cancer efficacy exists among the distinct groups of these anti-CA215 Mabs.
The promoter of MEG3, which encodes the long non-coding RNA (lncRNA) MEG3, is often hypermethylated in acute myeloid leukemia (AML). Additionally, the Tet methylcytosine dioxygenase 2 gene (TET2) is frequently inactivated, which can lead to impaired DNA methylation and promote AML development. We examined the association between TET2 and MEG3 promoter hypermethylation in Hainan patients with AML. The expression of MEG3, TET2, miR-22-3p, and miR-22-5p was assessed in bone marrow samples from AML patients and healthy controls using real-time quantitative PCR. Using Sequenom MassARRAY technology, we compared MEG3 promoter methylation in AML patients and healthy controls. MEG3 expression was lower in AML patients than in the controls (P = 0.136). Moreover, there was greater methylation of MEG3 promoter in the AML patients than the controls (P < 0.05). Methylation of the MEG3 promoter correlated negatively with TET2 expression (P < 0.05, r < 0). Likewise there was a negative correlation between TET2 activity and MEG3 promoter methylation (P < 0.05, r < 0). These results suggest that hypermethylation of the MEG3 promoter in AML may result from decreased TET2 activity. These data provide insight into the molecular mechanisms underlying AML development and progression.
PurposeChronic obstructive pulmonary disease (COPD) is predicted to become the third most common cause of death and the fifth most common cause of disability in the world by 2020. Recently, variants in the hypoxia-inducible factor 1α (HIF1A), cholinergic receptor, neuronal nicotinic, alpha polypeptide-5, and iron-responsive element-binding protein 2 gene (IREB2) genes were found to be associated with COPD. This study aims to identify whether the variations in these genes are related to COPD in the Hainan population of the People’s Republic of China.Patients and methodsWe genotyped 12 single nucleotide polymorphisms in a case-control study with 200 COPD cases and 401 controls from Hainan, People’s Republic of China. Odds ratios and 95% confidence intervals were estimated using the chi-squared (χ2) test, genetic model analysis, haplotype analysis, and stratification analysis.ResultsIn the genetic model analysis, we found that the genotype T/T of rs13180 of IREB2 decreased the COPD risk by 0.52-fold (P=0.025). But in the further stratification analysis, we failed to find the association between the selected single nucleotide polymorphisms with COPD risk in Han population. In addition, the haplotype analysis of HIF1A gene also was not found to be the possible haplotype associated with COPD risk.ConclusionOur results support that IREB2 rs13180 is associated with COPD in Hainan population. And this is the first time the HIF1A polymorphisms in COPD in a Chinese population has been reported, although we failed to find any significant result.
The high prevalence of asthma in the Li ethnic group highlights the importance of asthma prevention and treatment in this population. Risk factors indentified in this study warrant special attention. Elevating public awareness about asthma in local communities will benefit the prevention of the disease.
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