ABSTRACT
Background: CC chemokine receptor 7 (CCR7) is a member of G-protein-coupled receptor family and mediates chemotactic migration of immune cells and different cancer cells induced via chemokine (C-C motif) ligand 19 (CCL19) or chemokine (C-C motif) ligand 21 (CCL21). Hence, the identification of blockade antibodies against CCR7 could lead to the development of therapeutics targeting metastatic cancer. Methods: CCR7 was purified and stabilized in its active conformation, and antibodies specific to purified CCR7 were screened from the synthetic M13 phage library displaying humanized scFvs. The in vitro characterization of selected scFvs identified two scFvs that exhibited CCL19-competitive binding to CCR7. IgG4's harboring selected scFv sequences were characterized for binding activity in CCR7+ cells, inhibitory activity toward CCR7-dependent cAMP attenuation, and the CCL19 or CCL21-dependent migration of CCR7+ cells. Results: Antibodies specifically binding to purified CCR7 and CCR7+ cells were isolated and characterized. Two antibodies, IgG4(6RG11) and IgG4(72C7), showed ligand-dependent competitive binding to CCR7 with KD values of 40 nM and 50 nM, respectively. Particularly, IgG4(6RG11) showed antagonistic activity against CCR7, whereas both antibodies significantly blocked the ligand-induced migration and invasion activity of CCR7+ cancer cells. Conclusions: Two antibody clones were successfully identified from a synthetic scFv-displaying phage library using purified recombinant CCR7 as an antigen. Antibodies specifically bound to the surface of CCR7+ cells and blocked CCR7+ cell migration. Particularly, 6RG11 showed antagonist activity against CCR7-dependent cAMP attenuation.
ABSTRACT
OBJECTIVE: The aim of this study was to assess the association of chewing ability to oral health-related quality of life (OHRQoL) measured by the Oral Health Impact Profile-14 (OHIP-14) controlling for clinical oral health status, self-reported health status, demographic factors, and socioeconomic conditions among community-dwelling and institutionalized Korean elders. METHODS: This cross-sectional study comprised a sample of 307 community-dwelling and 102 institutionalized people over the age of 60, using a cluster sampling procedure. A questionnaire was implemented and a clinical oral examination was completed for each subject. The outcome variable of interest was the OHIP-14 score, and its associations with chewing ability, objective oral health status, self-reported health status, demographic factors, and socioeconomic conditions were assessed. Because of highly-skewed distribution of the OHIP-14 scores, nonparametric analytic methods were used. The final model was developed using a multivariable two-level logistic regression model for a dichotomized OHIP-14 score to account for the cluster sampling method applied to this study. RESULTS: The mean age of the participants was 75.4 years, with 67.7% being women. The median OHIP-14 score was 7. Negative oral health impacts were experienced fairly often or very often by a total of 36.4% of elderly. In the final model, elders who could chew none to three and four to six foods among seven indicator foods were 3.4 (P = 0.010) and 2.0 (P = 0.040) times more likely, respectively, to have worse OHRQoL compared with elders who could chew all seven food types. Also significant associations with worse OHRQoL were shown for being concerned about oral health [Odds Ratio (OR) = 4.9, P = 0.002], fair or better self-reported oral health (OR = 0.12, P = 0.002), very good/good self-reported general health (OR = 0.38, P = 0.008), being married (OR = 2.0, P = 0.054), and having a favourable economic status (OR = 0.43, P = 0.042). CONCLUSIONS: This study showed highly significant association between chewing ability and OHRQoL measured by the OHIP-14 score after controlling for related factors. Amelioration of chewing ability might independently contribute to improving the OHRQoL of elders.
