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      Radiosensitizing glioblastoma in a rat model using l-buthionine-sr-sulfoximine (BSO)

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      ataelmannan.pdf (898.3Kb)
      Date
      2008-04-21
      Author
      Ataelmannan, Khalid Ali
      Type
      Thesis
      Degree Level
      Masters
      Metadata
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      Abstract
      Glioblastoma multiforme (GBM) is the most aggressive and most common primary brain tumor in adults accounting for 50-60% of primary brain tumors. The prognosis for patients with GBM remains poor and treatment is mainly palliative with a mean survival time of less than one year. Radiotherapy is used extensively in the management of glioblastoma either alone or in combination with surgery and/or chemotherapy. However, this tumor is one of the most resistant tumors to radiotherapy thus limiting the benefit of this form of treatment. Studies have shown that malignant tumors have a high content of glutathione an antioxidant responsible for protecting the cells against damage from free radicals (mainly superoxide, hydroxyl and hydrogen peroxide). It is well established that glutathione, by neutralizing these free radicals plays a major role in radioresistance. Glioblastoma has relatively high levels of glutathione. In this study, by reducing the glutathione content of glioblastoma in a rat model, we were able to investigate the effect of this reduction in enhancing the effect of radiotherapy as a form of treatment for glioblastoma multiforme in a rat model. By injecting L-Buthionine-SR-Sulfoximine (BSO) in to the tumor tissue, the glutathione content of the tumor was reduced by about 70% of its initial value. When administered into the tumors 2 hours prior to radiotherapy the animals so treated had a significantly longer median survival time compared with animals that received radiotherapy alone.
      Degree
      Master of Science (M.Sc.)
      Department
      Surgery
      Program
      Surgery
      Supervisor
      Juurlink, Bernhard H. J.; Griebel, Robert W.
      Committee
      Keith, Roger G.; Fourney, Daryl; Chapman, L. Dean; McFadden, Andrew; Vachhrajani, Haresh
      Copyright Date
      April 2008
      URI
      http://hdl.handle.net/10388/etd-04202008-213437
      Subject
      l-buthionine-sr-sulfoximine
      rat
      glioblastoma
      radiosensitizer
      radiotherapy
      glutathione
      C6 glioma cell line
      bso
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