Apoptin gene therapy in head and neck cancer

Schoop, R.A.L.

Because of the disappointing progress that has been made in the last decades in survival in patients with head and neck cancer, existing therapy needs to be improved and/or new treatment needs to be introduced. This thesis describes a new promising treatment, apoptin gene therapy. The scope of this study was to investigate the applicability of apoptin in head and neck squamous cell carcinoma (HNSCC). First, we assessed its potential in-vitro. Next, a suitable animal model was established, which was used for in-vivo experiments with apoptin. In chapter 2 we describe the results of apoptin treatment in a HNSCC cell line with a mutated p53 and the effect of over-expression of Bcl-xL on the outcome. Chapter 3 describes the synergistic effect of apoptin and irradiation in HNSCC both in radiation sensitive and in more radioresistant HNSCC cell lines. The applicability of an immune competent animal model for in-vivo research is described in chapter 4. The time needed to establish a useful...Show moreBecause of the disappointing progress that has been made in the last decades in survival in patients with head and neck cancer, existing therapy needs to be improved and/or new treatment needs to be introduced. This thesis describes a new promising treatment, apoptin gene therapy. The scope of this study was to investigate the applicability of apoptin in head and neck squamous cell carcinoma (HNSCC). First, we assessed its potential in-vitro. Next, a suitable animal model was established, which was used for in-vivo experiments with apoptin. In chapter 2 we describe the results of apoptin treatment in a HNSCC cell line with a mutated p53 and the effect of over-expression of Bcl-xL on the outcome. Chapter 3 describes the synergistic effect of apoptin and irradiation in HNSCC both in radiation sensitive and in more radioresistant HNSCC cell lines. The applicability of an immune competent animal model for in-vivo research is described in chapter 4. The time needed to establish a useful oral squamous cell carcinoma in mice is assessed and immunological comparisons are made with human counterparts. In chapter 5 the tumorigenesis of the same carcinogenic immune competent model is investigated and characteristics are analyzed. The efficacy of the apoptin therapy in-vivo is described in chapter 6. This is done by looking into the effect of intratumoral injection of a constructed adenovirus expressing the apoptin protein. Finally, the data are critically discussed in chapter 7 in view of apoptin as a potential new anti-cancer therapy.Show less

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Apoptin gene therapy in head and neck cancer