Browsing by Subject "Viral vectors"
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- PublicationOpen AccessGene therapy strategies for intracranial tumours, glioma and pituitary adenomas(Murcia : F. Hernández, 2000) Castro, M.G.; Cowen, R.; Smith-Arica, J.; Williams, J.; Ali, S.; Windeatt, S.; Gonzalez-Nicolini, V.; Maleniak, T.; Lowenstein, P.R.Intracranial tumours such as brain gliomas and pituitary adenomas pose a challenging area of research for the development of gene therapy strategies, both from the point of view of the severity of the diseases, to the physiological implication of gene delivery into the central nervous system and pituitary gland. On the one hand, brain gliomas are very malignant tumours, with a life expectancy of six months to a year at the most after the time of diagnosis, in spite of advances in treatment modalities which involve chemotherapy, surgery and radiotherapy. Gene therapy for these tumours is therefore a very attractive therapeutic modality which due to the severity of the disease is already in clinical trials. On the other hand, pituitary tumours are usually benign, and in most cases, treatment is successful. Nevertheless, there are some instances, especially with the macroadenomas and some invasive tumours in which treatment fails. Gene therapy strategies for these adenomas therefore needs to progress substantially in terms of safety, adverse side effects and physiological impact on the normal pituitary gland before clinical implementation. In this paper, we will review gene delivery systems both viral and non-viral and several therapeutic strategies which could be implemented for the treatment of these diseases. These include cytotoxic approaches both conditional and direct, immune-stimulatory strategies, anti-angiogenic strategies and approaches which harness pro-apoptotic and tumour suppressor gene targets. We will also review the models which are currently available in which these gene therapy strategies can be tested experimentally. This new therapeutic modality holds enormous promise, but we still need substantial improvements both from the delivery, efficacy and safety stand points before it can become a clinical reality.
- PublicationOpen AccessPerspectives in gene therapy(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 1998) Martín Duque, Mª del P.; Sánchez Prieto, R.; Lleonart, M.; Ramón y Cajal, S.Gene therapy is understood to be both the restitution of genetic alterations caused by mutation or deletion and the control of overexpressed genes. The concept of gene therapy can also encompass molecular strategies to induce cell death in tumor cell by either the so-called "suicided genes" or by certain viral genes that induce a more selective cell dea th among th e transformed cells. The prospect for the clinical application of gene therapy are enormous and, at least theoretically. its utilization can be extended to a number of diseases known to have a genetic basis, and to neoplastic processes. This review summarizes some of the projects that are currently underway involving neopla stic dise ases. liver disease s, hematopoi e tic cells and respiratory tract cells. The results of most of the ongoing protocols are not yet conclusive, and presumibly, their clinical application is still some years away. One of the major limitations is the method of introducing the ge ne tic sequences into the cells and achieving their constitutive expression by the cells. For ethical reasons, this approach should not be done in germ cells, but at the leve l of the tissue or cells most closely involved in the deve lopment of each gene-based disease. The methods employed in gene therapy are discussed, focusing on those med iated by the application of viral vectors, as well as those requiring the use of liposomes and others.