No abstract

Human retinoblastomas are malignant intraocular tumors and have a high incidence in children. Chemotherapy combined with local therapy is the principal means of retinoblastoma treatment, the application of which has saved the eye of many children and avoided external irradiation. UNBS5162, a naphthalimide, has broad prospects as a tumor treatment, with fewer toxic side effects and higher cancer-suppression efficiency. However, the efficacy of UNBS5162 in human retinoblastomas is still not clear. In the present study, we investigated the specific mechanism of UNBS5162 in the human retinoblastoma cell lines WERIRb1 and Y79. Compared with a negative-control (NC) group, UNBS5162 treatment for 72 hours significantly decreased cell proliferation; meanwhile, more apoptotic cells were observed in the UNBS5162-treated group (27.1% in WERIRb1, 20.83% in Y79) than in the NC group (11.59% in WERIRb1, 12.89% in Y79). We also found caspase 3 p17 and Bax expression to be upregulated and Bcl2 downregulated significantly in UNBS5162-treated WERIRb1 and Y79 cells. The effects of UNBS5162 on human retinoblastoma cells may be regulated by the Akt–mTOR pathway. We found expression of the Akt pathway and key proliferation-related genes – those for p-Akt, p-mTOR, p70, and cyclin D1 – were downregulated significantly in the UNBS5162-treated group compared with the NC group in WERIRb1 and Y79. Therefore, for the first time, we demonstrated that UNBS5162 can inhibit proliferation and promote apoptosis of human retinoblastoma cells by regulating activity of the Akt–mTOR pathway in vitro, suggesting the potential value of UNBS5162 in treatment for human retinoblastoma.

Adenocarcinoma (ADC) and squamous cell carcinomas (SCC) are two subtypes of non small cell lung carcinomas which are regarded as the leading cause of cancer related malignancy worldwide. The aim of this study was to detect the differentially methylated loci (DML) and differentially methylated genes (DMGs) of these two tumor sets, and then to illustrate the different expression levels of specific methylated genes. Using the TCGA database and Illumina HumanMethylation27 arrays, we first screened the DMGs and DML in tumor samples. Then, we explored the Biological Process terms of hypermethylated and hypom ethylated genes using Functional Gene Ontology (GO) catalogues. Hypermethylation intensively occurred in the CpG island, whereas hypomethylation was located in the non CpG island. Most SCC and ADC hypermethylated genes involved GO function of DNA dependent regulation of transcription, and hypome thylated genes mainly enriched in the term of immune responses. Additionally, the expression levels of spe cific differentially methylated genes are distinct between ADC and SCC. It was concluded that ADC and SCC have a different methylation status that might play an important role in carcinogenesis.