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العنوان
Gene therapy for head and neck cancer /
المؤلف
Abu khalil, Mahmoud Mohamed.
هيئة الاعداد
باحث / محمود محمد أبوخليل
مشرف / محمد عبدالحليم الصديق
مشرف / يوسف كامل حسن شبانة
مناقش / محمد عبدالحليم الصديق
الموضوع
Otorhinolaryngologic Diseases - genetics. Otolaryngology - Genetic aspects. Gene Therapy - trends.
تاريخ النشر
2004.
عدد الصفحات
123 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
علم الأورام
تاريخ الإجازة
1/1/2004
مكان الإجازة
جامعة المنصورة - كلية الطب - الأذن والأنف والحنجرة
الفهرس
Only 14 pages are availabe for public view

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Abstract

The increasing knowledge of cancer molecular biology has led to the development of new genetic therapies with the potential to target tumors selectively. In squamous cell cancer of the head and neck, such therapies may be beneficial in the treatment and prevention of loco­regional recurrence, a disease with considerable mortality and morbidity, by direct injection of the tumor or surgical resection margins and bed. Results from early clinical trials are encouraging and are now entering the next stage of clinical trial development. These therapies are so far dependent upon direct intratumoral injection, since systemic injection is currently limited by the immune mediated elimination of the viral vectors used for gene transduction. This is the main disadvantage of currently available genetic therapies. In squamous cell cancer of the head and neck cancer, 25% of patients with stage III or IV disease will have minimal residual disease at distant sites at presentation. Thus, a systemic form of gene therapy would be extremely valuable for this disease. Therefore, much work is being carried out to develop better vectors, which are able to evade the immune system, in order to allow longer transgene expression and to allow repeated administration of the therapy. Examples of this are to use viruses with non­erossreactive serotypes, or by creating viruses, which are encapsulated in, polylactic­glycolic acid copolymer (PLGA) to evade the immune system. It is also possible to suppress any antibody response using y­ interferon and IL­12. Other recent research to avoid the problems of the immune system has involved the use of human artificial chromosomes (HAC). These are high molecular weight DNA segments up to 1 Mb in size which can now be made using yeast methodology. Such high molecular weight DNA can contain several genes with their respective promoters rather than single transgenes and they can be transfected into cells using lipid vectors. Another area of research is in the development of viral vectors, which are chimeras of retroviruses and adenoviruses. These give more efficient gene transfection (a property of adenoviral vectors) and give longer transgene expression by integration of the transgene into the host cell genome (a property of retroviruses). Such vectors therefore have the best of both worlds though these vectors would still have to be modified to evade early elimination by the host immune system.