Rabbit Anti-Human CBL (C-terminal) Polyclonal antibody

Introduction This study is an extended follow-up of a randomized controlled trial that evaluated 18-month outcomes following free gingival grafts (FGGs) around implants with <2 mm keratinized mucosa (KM) compared to implants without KM augmentation. Materials and Methods Follow-up data were obtained over 48 months from 18 implants in the FGG group (11 subjects) and 8 implants in the no-surgery group (7 subjects) within the control group. FGGs were performed after 18 months for 8 implants in the control group; these 8 implants constituted a delayed FGG group (5 subjects). The width of KM, mucosal recession (MR) and crestal bone level (CBL) were obtained. Results The increased width of KM and the reduced MR following FGGs were maintained for 48 months in the FGG group, which exhibited less MR than the no-surgery group. The amount of crestal bone loss (0.4 +/- 0.4 mm) in the no-surgery group was significantly greater than that in the FGG group (0 +/- 0.4 mm) at 48 months. In the delayed FGG group, reduced MR and no significant differences in CBL were observed compared with the pre-graft measurements. Conclusions FGGs can be a practical treatment option to maintain CBL around implants with limited KM.

Epidermal growth factor receptor (EGFR) is highly expressed in head and neck squamous cell carcinoma (HNSCC) and related to cancer progression. The resistance to anti-EGFR therapy remains a major clinical problem in HNSCC. In this study, we found that TOLL-like receptor 4 (TLR4) was highly expressed in 50% of EGFR overexpressed HNSCC biopsies, which correlated to worse prognosis in patients. In HNSCC cell lines, activation of TLR4 reversed cetuximab-induced the inhibition of proliferation, migration and invasion. LPS induced of TLR4 signaling was potentiated under cetuximab treatment, showing increased activation of downstream NF-kappa B and MAPK pathways. Accordingly, cetuximab treatment also increased expression of TNF-alpha, COX2, and other molecules involved in TLR4 induced tumor inflammation. Mechanistically, we found inhibition of EGFR by cetuximab led to decreased phosphorylation of Src and sequentially Src-medicated activation of Cbl-b. This inhibited Cbl-b-mediated degradation of the key TLR4 adaptor protein MyD88 and activated TLR4 signaling. TLR4 or MyD88 overexpressed CAL27 and SCC4 cells grew faster and were more resistant to cetuximab and gefitinib both in vitro and in vivo. Out study delineates a crosstalk between EGFR and TLR4 pathways and identified TLR4 as a potential biomarker as well as a therapeutic target in overcoming the resistance to anti-EGFR therapy of HNSCC.