Anti-EGF polyclonal antibody

Disulfide bonds typically introduce conformational constraints into peptides and proteins, conferring improved biopharmaceutical properties and greater therapeutic potential. In our opinion, disulfide-rich microdomains from proteins are potentially a rich and under-explored source of drug leads. A survey of the UniProt protein database shows that these domains are widely distributed throughout the plant and animal kingdoms, with the EGF-like domain being the most abundant of these domains. EGF-like domains exhibit large diversity in their disulfide bond topologies and calcium binding modes, which we classify in detail here. We found that many EGF-like domains are associated with disease phenotypes, and the interactions they mediate are potential therapeutic targets. Indeed, EGF-based therapeutic leads have been identified, and we further propose that these domains can be optimized to expand their therapeutic potential using chemical design strategies. This Review highlights the potential of disulfide-rich microdomains as future peptide therapeutics.

Regional metastasis is the single most important prognostic factor in oral squamous cell carcinoma (OSCC). Abnormal expression of N-myc downstream-regulated genes (NDRGs) has been identified to occur in several tumor types and to predict poor prognosis. In OSCC, the clinical significance of deregulated NDRG expression has not been fully established. In this study, NDRG1 relevance was assessed at gene and protein levels in 100 OSCC patients followed up by at least 10 years. Survival outcome was analyzed using a multivariable analysis. Tumor progression and metastasis was investigated in preclinical model using oral cancer cell lines (HSC3 and SCC25) treated with epidermal growth factor (EGF) and orthotopic mouse model of metastatic murine OSCC (AT84). We identified NDRG1 expression levels to be significantly lower in patients with metastatic tumors compared with patients with local disease only (P = 0.001). NDRG1 expression was associated with MMP-2, -9, -10 (P = 0.022, P = 0.002, P = 0.042, respectively) and BCL2 (P = 0.035). NDRG1 lower expression was able to predict recurrence and metastasis (log-rank test, P = 0.001). In multivariable analysis, the expression of NDRG1 was an independent prognostic factor (Cox regression, P = 0.013). In invasive OSCC cells, NDRG1 expression is diminished in response to EGF and this was associated with a potent induction of epithelial-mesenchymal transition phenotype. This result was further confirmed in an orthotopic OSCC mouse model. Together, this data support that NDRG1 downregulation is a potential predictor of metastasis and approaches aimed at NDRG1 signaling rescue can serve as potential therapeutic strategy to prevent oral cancer progression to metastasis.