“Introduction Nasopharyngeal

carcinoma (NPC) is on


“Introduction Nasopharyngeal

carcinoma (NPC) is one of highly prevalent, most harmful malignant tumors in Southern China and RGFP966 research buy Southeast of Asia. It is caused by the interaction between genetic background and environmental factors such as Epstein-Barr virus. At present, radiotherapy and/or induction chemotherapy is the mainstay of treatment modalities. Despite continuously progress in radiotherapeutic equipment and technology, see more the 5-year survival rate of NPC remains about 50% without fundamental improvement over the past several decades. Understanding the etiology and developing new effective therapeutic modality are particularly important in NPC treatment. Suicide gene therapy is a promising modality for cancer treatment. Such PLX-4720 datasheet therapy introduces a drug susceptible gene such as herpes simplex virus thymidine kinase (TK) gene into tumor cells. Expressed TK phosphorylates its substrate, a nontoxic prodrug ganciclovir (GCV), leading to accumulation of the toxic ganciclovir triphosphate and cell apoptosis. The ideal suicide gene expression constructs should have high specificity and killing efficacy to tumor cells. To selectively introduce suicide gene into tumor cells, many tumor specific promoters have been employed to construct tumor-specific suicide gene expression vectors. Human telomerase reverse transcriptase (hTERT), the core component of telomerase, plays

important roles in vast majority of malignant tumors including nasopharyngeal carcinoma. The telomerase activity and level of hTERT expression are enhanced in all nasopharyngeal carcinoma cell lines and 88% nasopharyngeal tissues. Their

activities are closely correlated with clinical Liothyronine Sodium biological characteristics of nasopharyngeal carcinoma[1, 2]. Therefore, telomerase/hTERT is utilized as a targeted gene for treatment of nasopharyngeal carcinoma and its promoter has been widely employed to drive the tumor-specific expression of exogenous genes. For example, Wang et al[3] and Zhang et al [4] constructed vectors pGL3-hTp-TK/GCV and TERT-E1A-TK, respectively, both of which can kill lung cancer cells and transplanted tumor in vitro and in vivo. Zheng et al [5] constructed vector pHSV-TK/CRAD, which can significantly enhance the killing effect of GCV on liver cancer in animal. Shen et al [6] selectively expressed shRNA in nasopharyngeal carcinoma cells by introducing hTERT, which successfully inhibited telomerase activity and induced cell apoptosis. We [7] have reported previously that administration of antisense oligodeoxynucleotide of telomerase RNA (hTR) and hTERT subunit can inhibit telomerase in tumor cells and induce tumor cell apoptosis. Recently, we [8, 9] exploited the hTERT promoter to construct pGL3-hTERTp-TK vector and introduced the vector into NPC tumor cells in vitro and in vivo in mice xenograft, which killed NPC tumor cells and xenograft without observing toxicity to liver and kidney.

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