Increasing Cerebrovascular Permeability to Facilitate Brain Tumor Therapy

  • 嚴 家慶

Student thesis: Master's Thesis


Glioblastoma Multiforme (GBM) is the most common and the most fast-growing type of malignant brain tumor in clinical It is a fatal cancer with high invasion and infiltration of the surrounding normal tissue In addition the GBM patients’ average survival rate is only 12-15 months and they also show poor functional health status The current standard treatment is surgical resection radiotherapy and chemotherapy However even if the patients receive these standard treatments this median survival for adults only increases by about 10% increasing the average survival rate to two years Medical treatments for GBM also face several challenges As the tumor is spread throughout the brain tissue surgical resection is not able to completely remove it In addition the blood brain barrier (BBB) presents another challenge preventing or limiting many chemotherapeutics from entering the brain tissue thus affecting the drug delivery and effect in the tumor Currently new anti-cancer drugs such as Temozolomide (TMZ) or Bevacizumab (Avastin) have been developed which are able to penetrate the BBB more easily However these drugs still have some side effects such as hypertension fatigue and diarrhea In this study we provide a new direction to improve anticancer drug permeability through the BBB and enhance the therapeutic effects by pre-treatment with vascular endothelial growth factor-A165 (VEGF-A165) The results demonstrate that pre-treatment with VEGF-A165 could help drugs to penetrate the BBB and thus enhance drug delivery and reduce side effects Using Evans blue and a nanoparticle-based system we also show that pre-treatment with VEGF-A165 can temporarily increase BBB permeability and thus the ratio of dye and nanoparticles penetrate into the brain Furthermore we also show that pre-treatment with VEGF-A165 followed by TMZ significantly reduces the tumor size and prolongs the mean survival rate of mice with glioblastoma compared to TMZ alone In summary we believe that the results of this study provide a new direction for the future of brain tumor therapy
Date of Award2014 Sep 2
Original languageEnglish
SupervisorKuen-Jer Tsai (Supervisor)

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