Head and neck squamous cell carcinoma (HNSCC) exhibits increased expression of cyclin D1 (CCND1). Previous studies have shown a correlation between poor prognosis of HNSCC and cyclin D1 overexpression. tRNase ZL-utilizing efficacious gene silencing (TRUE gene silencing) is one of the RNA-mediated gene expression control technologies that have therapeutic potential. This technology is based on a unique enzymatic property of mammalian tRNase ZL, which is that it can cleave any target RNA at any desired site by recognizing a pre-tRNA-like complex formed between the target RNA and an artificial small guide RNA (sgRNA). In this study, we designed several sgRNAs targeting human cyclin D1 mRNA to examine growth inhibition of HNSCC cells. Transfection of certain sgRNAs decreased levels of cyclin D1 mRNA and protein in HSC-2 and HSC-3 cells, and also inhibited their proliferation. The combination of these sgRNAs and cisplatin showed more than additive inhibition of cancer cell growth. These findings demonstrate that TRUE gene silencing of cyclin D1 leads to inhibition of the growth of HNSCC cells and suggest that these sgRNAs alone or combined with cisplatin may be a useful new therapy for HNSCCs.
ABSTARACTConclusion. Grade≧3 mucositis/stomatitis and inability to feed orally were problematic for patients undergoing cetuximab-based bioradiotherapy (BRT) as well as platinum-based chemoradiotherapy (CRT). Severe mucositis/stomatitis and radiation dermatitis should be addressed carefully in patients undergoing cetuximab-based BRT as well.Objectives. The efficacy of cetuximab-based BRT in locally advanced head and neck squamous cell carcinomas has been established. However, the safety of cetuximab-based BRT in comparison with platinum-based CRT is currently under investigation.Method. We retrospectively analyzed 14 patients undergoing cetuximab-based BRT and 29 patients undergoing platinum-based CRT to compare the incidence of acute toxicities.In BRT group, an initial cetuximab loading dose of 400 mg/m 2 was delivered one week before the start of radiotherapy. Seven weekly infusions of 250 mg/m 2 of cetuximab followed during the definitive radiotherapy. In CRT group, cisplatin was administered at a dose of 40mg/m 2 weekly during the definitive radiotherapy.Results. The BRT group had a higher incidence of Grade≧3 radiation dermatitis than did the CRT group (36% vs 3%, respectively, p<0.01). The incidence rate of Grade≧3 mucositis/stomatitis was 64.3 % and 41.4% in the BRT and CRT group, respectively (p=0.1484), while the incidence rate of the inability to feed orally was 38.5% and 55.2%, respectively (p=0.2053).
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