多型性神經膠母細胞瘤是一種臨床上最常見且生長速度很快的惡性腦瘤，它也是一種具高度組織侵略性和浸潤性的致命癌症。此外，多型性神經膠母細胞瘤的病人平均存活率只有12到15個月，其生活機能狀態也較差。目前多型性神經膠母細胞瘤標準的治療方式是以手術、放射線治療與化療為主。然而，即使病人接受了標準的治療療程，其兩年平均存活率也僅上升了10％。另一方面，藥物治療也遇到了許多挑戰。而當腫瘤擴散到其他腦組織時，手術的方式將無法徹底的清除腫瘤。此外，血腦障壁的存在則是另一個挑戰，它防止且限制了許多藥物進入到腦組織，從而影響到藥物在腫瘤的傳遞與作用。目前儘管許多抗癌藥物像是帝盟多(Temozolomide)與癌思停(Bevacizumab)較能穿過血腦障壁，這些藥物也造成了許多副作用，像是高血壓、疲勞與腹瀉。
在我的論文研究中，我們提供了一個新的思考方向--藉由血管生長因子(VEGF-A165)的前處理去改善抗癌藥物在血腦障壁的通透性與治療效果。我們的實驗結果證明了預先給予血管生長因子可以幫助藥物通過血腦障壁，進而增加了抗癌藥物的傳遞並降低了副作用。在伊文思藍(Evans blue)與奈米粒子的系統中，我們也證明了預先給予血管生長因子可以暫時性的增加血腦障壁的通透性，進而增加了伊文思藍與奈米粒子進入到腦組織中的比率。此外，我們也證明了預先給予血管生長因子再給予藥物跟單純只給予藥物的組別相比，可以明顯減少腫瘤體積、並且延長腫瘤老鼠的存活率。綜合以上結果，我們相信這項研究結果提供了未來腦瘤治療的新方向。

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.

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