A novel approach to glioma therapy using an oncolytic adenovirus with two specific promoters

Abstract

Abstract. Gliomas are the most common type of primary brain tumor in adults, where more than half of the cases are malignant, and the prognosis is poor. The early viral 1A (E1A) protein has been widely recognized to be essential for adenoviral replication and production of progeny virions in human cells, a process that is regulated by human telomerase reverse transcriptase. The p53 gene, as a tumor suppressor, regulates diverse cellular processes, including cell cycle arrest, cell autophagy, senescence and apoptosis. Dysfunction of the p53 pathways is common in malignant gliomas. Exogenous expression of p53 during adenovirus replication in human cancer cells may accelerate cell death and improve the release of early virus progeny. In the present study, a conditionally replicative adenovirus (CRAd) Ad-Tp-E1A-Gp-p53, which expressed functional p53 protein when replicating in cancer cells, was constructed. Next, the level of p53 expression in U251 cells was determined by western blot analysis, and the inhibitory effect of Ad-Tp-E1A-Gp-p53 on U251 cells was detected via an MTT assay. The results indicated that p53 expression was upregulated with an increase in the multiplicity of infection (MOI) of Ad-Tp-E1A-Gp-p53. Additionally, the inhibitory effects of Ad-Tp-E1A-Gp-p53 in different groups were significantly different (P<0.05), with the inhibition ratio of the experimental groups being higher, compared with the control group (P<0.05). Furthermore, the inhibition ratio increased with increases in the MOI of Ad-Tp-E1A-Gp-p53. Therefore, the expression of functional p53 and that of E1A may increase the potency of CRAd, and overexpression of p53 through CRAd is a promising approach to more effective treatments in a number of human cancer types.

Absent in melanoma 2 enhances anti‐tumour effects of CAIX promotor controlled conditionally replicative adenovirus in renal cancer

“…Tumour-specific promotors can control the expression of viral genes or therapeutic genes to select replication in tumour cells instead of normal cells. 9,10 The cell surface protein, carbonic anhydrase IX (CAIX), is a tumour-sassociated antigen of renal cancer. 11 CAIX expression is almost not detected on normal kidney cells or other normal cells, but an increasing expression is detected on 90% of renal cancer lesions.…”

“…Tumour‐specific promotors can control the expression of viral genes or therapeutic genes to select replication in tumour cells instead of normal cells 9,10 . The cell surface protein, carbonic anhydrase IX (CAIX), is a tumour‐sassociated antigen of renal cancer 11 .…”

Effect of modulation of epithelial‑mesenchymal transition regulators Snail1 and Snail2 on cancer cell radiosensitivity by targeting of the cell cycle, cell apoptosis and cell migration/invasion (Review)

“…Based on these data, cancer can be considered as a significant public health issue worldwide, and thus requires intense research into the improvement of prevention strategies and enhancing the effectiveness of treatment. Numerous types of curative therapy, including chemotherapy (4), gene therapy (5), radiotherapy and immunotherapy (6,7), are used to treat cancer. Radiotherapy is an effective and commonly employed treatment in the management of >50% of human malignancies and remains a standard therapeutic modality for cancer patients (8,9).…”

Effect of therapies-mediated modulation of telomere and/or telomerase on cancer cells radiosensitivity

“…Based on the data enumerated above, cancer can be considered as an important public health which needs the strong strategies of management for its prevention and its treatment. Moreover, many kinds of strategies of treatment such as chemotherapy [ 2 ], immunotherapy [ 3 ], genetherapy [ 4 ], nanotherapy [ 5 ], radiotherapy [ 6 ], phytotherapy [ 7 ] have been developed and used to treat cancer. Among all strategies mentioned above, Radiotherapy seems more important because, in many countries, more than 50% of new cases of cancer received at least one course of radiotherapy during their lifetime [ 8 , 9 ].…”