The role of the bystander effect in suicide gene therapy
| Autor: | Graeme J. Poston, Anne R Kinsella, I.M. Pope |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Cancer Research
Genes Viral Antimetabolites Colorectal cancer Genetic enhancement Genetic Vectors Malignancy Thymidine Kinase law.invention Mice law Neoplasms Chromosome instability Animals Simplexvirus Medicine Prodrugs Ganciclovir Gene Cell Death Oncogene business.industry Genetic Therapy Suicide gene medicine.disease Combined Modality Therapy Rats Oncology Immunology Cancer research Cytokines Suppressor business |
| Zdroj: | European Journal of Cancer. 33:1005-1016 |
| ISSN: | 0959-8049 |
| DOI: | 10.1016/s0959-8049(96)00483-2 |
| Popis: | INTRODUCTION IN RECENT years, a combination of cytogenetic and molecular techniques has allowed the identification of the precise genetic alterations that underlie the stepwise progression to malignancy. This is particularly true of colorectal carcinoma, and the genetic events associated with key stages in the clonal progression, from normal colonic mucosa through early and late adenomatous changes to localised malignancy, have been clearly identified [l-3]. Attempts have been made to explollt this knowledge to develop new therapeutic strategies for the treatment of patients with cancer, and a number of exlperimental approaches to ‘cancer gene therapy’ have been described. These include strategies designed to suppress the expression of an oncogene or to restore the function of a defective tumour suppressor gene. Alternative approaches involve either strategies designed to enhance an antitumour immune response or the insertion of genes conferring drug resis#tance or drug sensitivity. The identification and precise sequencing of oncogenes has led to the development of antisense strategies for cancer gene therapy. These therapies aim to suppress the expression of a specific oncogene. Antisense oligonucleotides are short sequences of REi’A that are complementary to cellular mRNA oncogene 1:ranscripts. Antisense transcripts bind to oncogene mRNA and thereby inhibit mRNA translation. In several in vitro models, this has resulted in the inhibition of proliferation and reversal of the malignant phenotype [4, 51. Mutations of tumour suppressor genes also contribute to the development of malignancy. Indeed, mutation of the tumour suppressor gene TP53 is the most common genetic alteration in human malignancy [6-81. One of the prime functi0n.s of wild-type TP53 is thought to be the prevention of DNA damage accumulation and chromosomal instability that may predispose tumour formation. A further approach to cancer gene therapy, therefore, involves the restoration cd a defective tumour suppressor gene. In vitro, the transduction of wild-type TPS3 has been shown to arrest the growth of a colorectal carcinoma cell line [9] and in viva, wild-type TP53 has prevented tumour |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect