Inhibiting Notch activity and brain tumor progression using Zen Sheng Ping (ZSP)

描述（由申请方提供）：本提案的目的是确定恶性脑肿瘤是否对中草药制剂Zen Sheng Ping（ZSP，也称为抗肿瘤B）敏感。ZSP是六种草药的组合，已被证明可以防止食管癌前病变的进展。它似乎还可以减缓或预防人类和动物模型中肺癌的进展。最近发现ZSP下调肺癌中的Notch信号通路。Notch通路在肺肿瘤细胞增殖中起关键作用，表明Notch抑制是ZSP介导抗肿瘤作用的重要机制。这增加了ZSP也可能成功治疗其他Notch依赖性肿瘤的可能性。我们已经证明Notch信号在几种类型的脑癌的生长中起着关键作用，包括儿童（成神经管细胞瘤）和成人（成胶质细胞瘤）中最常见的恶性脑肿瘤。其他可能使用ZSP治疗的Notch依赖性肿瘤包括胰腺癌、乳腺癌和卵巢癌以及黑色素瘤。小分子Notch抑制剂似乎通过耗尽干细胞样癌细胞来阻断脑肿瘤异种移植物的形成和生长，但这类化合物与显著的毒性相关。因此，我们计划研究ZSP是否可能通过阻断Notch活性来代表恶性脑肿瘤的更有效和/或毒性更小的治疗。项目叙述：该提案的目的是确定恶性脑肿瘤是否可以使用称为Zen Sheng Ping（ZSP）的中草药治疗。最近发现ZSP抑制癌细胞中称为Notch的重要分子途径。我们已经证明Notch信号在几种脑癌的生长中起着关键作用，包括儿童（成神经管细胞瘤）和成人（成胶质细胞瘤）中最常见的恶性脑肿瘤

DESCRIPTION (provided by applicant): The goal of this proposal is to determine if malignant brain tumors are sensitive to the Chinese herbal remedy Zen Sheng Ping (ZSP, also known as antitumor B). ZSP is a combination of six herbs which has been shown to prevent the progression of pre-neoplastic lesions of the esophagus. It also appears to slow or prevent progression of lung cancer in both humans and in animal models. It was recently found that ZSP downregulates the Notch signaling pathway in lung cancer. The Notch pathway plays a critical role in the proliferation of lung tumor cells, suggesting Notch inhibition is an important mechanism by which the anti-tumor effects of ZSP are mediated. This raises the possibility that ZSP might also successfully treat other Notch- dependant tumors. We have shown that Notch signaling plays a critical role in the growth of several types of brain cancer, including the most common malignant brain tumors in children (medulloblastoma) and adults (glioblastoma). Other Notch-dependent neoplasms that might be treated using ZSP include pancreatic, breast and ovarian carcinomas, as well as melanoma. Small-molecule Notch inhibitors appear block the formation and growth of brain tumor xenografts by depleting stem-like cancer cells, but this class of compounds has been associated with significant toxicity. We therefore plan to investigate whether ZSP might represent a more potent and/or less toxic treatment for malignant brain tumors by blocking Notch activity. Project Narrative: The goal of this proposal is to determine if malignant brain tumors can is treated using a Chinese herbal remedy known as Zen Sheng Ping (ZSP). It was recently found that ZSP inhibits an important molecular pathway known as Notch in cancer cells. We have shown that Notch signaling plays a critical role in the growth of several types of brain cancer, including the most common malignant brain tumors in children (medulloblastoma) and adults (glioblastoma)