Brain Cancer Zebrafish Xenotransplant Model for Drug Screening

描述（由申请人提供）：转移性脑肿瘤发生在大约10-30%的成人癌症中。许多形式的癌症可以扩散到大脑，最常见的是肺癌，乳腺癌，黑色素瘤，肾癌，膀胱癌，某些肉瘤，睾丸癌和其他一些癌症。成人最常诊断的原发性恶性脑肿瘤是多形性胶质母细胞瘤（GBM）。它占所有原发性脑肿瘤的约30%。GBM的特征性特征是它们快速增殖并侵入邻近组织，尽管很少转移到脑外。完全手术切除GBM是不可能的。胶质母细胞瘤患者的生存预后保持在约1年，尽管积极的手术，放射和化疗。脑癌治疗的主要障碍是血脑屏障（BBS）。大约98%的小分子药物和几乎所有的大分子药物都不能穿过这一屏障以有效靶向脑癌。此外，脑血管中存在主动外排机制，可将药物泵出大脑。目前还没有有效的体内模型系统来测试候选药物阻碍血脑肿瘤屏障的能力或降低脑癌化疗疗效的有效药物外排机制。该SBIR旨在开发一种斑马鱼异种移植模型，用于识别脑癌的潜在候选药物。该SBIR将评估胚胎发生、模式化、癌细胞增殖、药物穿过血脑屏障的能力及其对脑肿瘤的影响。

DESCRIPTION (provided by applicant): Metastatic brain tumors occur in approximately 10-30% of adult cancers. Many forms of cancer can spread to the brain, the most common being lung cancer, breast cancer, melanoma, kidney cancer, bladder cancer, certain sarcomas, testicular and a number of others. The most commonly diagnosed primary malignant brain tumor of adults is glioblastoma multiforme (GBM). It represents about 30% of all primary brain tumors. The characteristic features of GBM are that they proliferate rapidly and invade adjacent tissue although rarely metastasize outside the brain. Complete surgical removal of GBM is not possible. The prognosis for survival of patients with glioblastoma remains at approximately 1 year, despite aggressive surgery, radio- and chemotherapy. The main obstacle to treatment of brain cancer is the blood brain barrier (BBS). Approximately 98% of all small-molecule drugs and nearly all large- molecule drugs cannot cross this barrier to effectively target brain cancer. In addition active efflux mechanisms exist in brain vessels to pump drugs out of the brain. There is no efficient in vivo model system for testing drug candidates for their ability to thwart the blood brain tumor barrier or the efficient drug efflux mechanisms that reduce the efficacy of chemotherapy for brain cancer. This SBIR aims to develop a zebrafish xenograft model for identifying potential drug candidates for brain cancer. This SBIR will assess embryogenesis, patterning, cancer cell proliferation, the ability of drugs to cross the BBB and their effects on brain tumors.