DNA methyltransferases (DNMTs) 1, 3a, and 3b affect DNA promoter methylation; studies have suggested that they have important roles in the development of cancers. In this study, we analyzed the expression of DNMTs 1, 3a, and 3b; the MIB-1 labeling index; and their clinical significance in 6 normal retinas and 62 retinoblastomas using immunohistochemical analysis. We found that DNMT proteins were not expressed in normal retinas, whereas they were frequently expressed in retinoblastomas (DNMT1, 100%; DNMT3a, 98%; and DNMT3b, 92%). Compared with well-differentiated retinoblastomas, the expression of DNMTs 1 and 3a significantly increased in poorly differentiated retinoblastomas (P = .002 and P = .003, respectively); in addition, the frequency of their increased expression was high. DNMT1 expression was significantly higher in invasive retinoblastoma. Furthermore, the expression of DNMTs was positively correlated with the MIB-1 labeling index in retinoblastoma. Our findings suggest that the overexpression of DNMTs 1, 3a, and 3b may be related to retinoblastoma tumorigenesis and progression and may represent a novel approach for retinoblastoma therapy.

This study demonstrated that expression of RelA and c-Rel proteins represents a reliable prognostic marker of retinoblastoma and that NF-κB is related to retinoblastoma tumorigenesis and progression through a non-conventional pathway. This data suggests that therapeutic strategies targeting NF-κB combined with other therapies may represent a novel approach to retinoblastoma therapy.

The improved tumoricidal effect of the radioantibody mixture ("cocktail") has been reported recently for the treatment of colon tumor. In the present study, we demonstrated the enhanced radioimmunotherapeutic efficacy of a monoclonal antibody (MAb) cocktail against human hepatocellular carcinoma. Therapeutic efficacy was determined by measuring the change in tumor size over a period, determining the percentage of growth inhibition of each treatment at various times after radioantibody therapy.

Human Glutaredoxin3 (hGLRX3), which encodes a 37.4 kDa protein, possesses an N-terminal Trx homology domain followed by two tandem repeats of Grx domains. GLRX3 is expressed in many tissues and plays important roles in iron metabolism, antioxidant effect, cell proliferation and development, regulation of immune reaction, and tumorigenesis. The mechanisms underlying the biological function of GLRX3 are still not clear. To facilitate the functional research of GLRX3, in this study, monoclonal antibodies (MAbs) against hGLRX3 were produced by using purified prokaryotic recombinant 6His-hGLRX3 fusion protein as the immunogen. Five MAbs were obtained after preliminary screening by indirect enzyme-linked immunosorbent assay, then further characterized by Western blot analysis and immunocytochemistry. The domain specificity of these MAbs was also evaluated. Owing to the high conservation of protein sequences among different species, anti-GLRX3 MAbs produced in this study were shown to be immunoactive for GLRX3 in the cells from other species, such as mice, rats, Chinese hamster, and zebrafish. These domain-specific anti-GLRX3 MAbs will be an essential tool to investigate the roles of GLRX3 in normal physiological or pathological conditions.