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

使用禅生平 (ZSP) 抑制 Notch 活性和脑肿瘤进展

• 批准号: 7383042
• 负责人: Charles G Eberhart
• 金额: $ 24.6万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7383042
• 关键词: Adult Glioblastoma; Adult Medulloblastomas; Animal Model; Antitumor B; Brain Neoplasms; Breast; Child; Chinese Herbs; Class; Clinical; Engraftment; Esophagus; Glioblastoma; Goals; Growth; Herb; Human; Injection of therapeutic agent; Lesion; Lung Neoplasms; Malignant neoplasm of brain; Malignant neoplasm of lung; Mediating; Molecular; Neoplasm Metastasis; Neoplasms; New Agents; Notch Signaling Pathway; Ovarian Carcinoma; Pancreas; Pathway interactions; Patients; Play; Protocols documentation; Role; Signal Transduction; Simulate; Therapeutic; Toxic effect; Tumor Debulking; cancer cell; inhibitor/antagonist; medulloblastoma; melanoma; neoplastic; neoplastic cell; notch protein; prevent; research study; small molecule; stem; tumor; tumor growth; tumor progression; tumor xenograft

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)

描述（由申请人提供）：本提案的目的是确定恶性脑肿瘤是否对中药禅生平（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道肿瘤前病变的进展。在人类和动物模型中，它似乎也能减缓或预防肺癌的进展。最近发现ZSP在肺癌中下调Notch信号通路。Notch通路在肺肿瘤细胞的增殖中起着至关重要的作用，提示Notch抑制是ZSP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信号在几种脑癌的生长中起着关键作用，包括儿童（髓母细胞瘤）和成人（胶质母细胞瘤）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抑制剂似乎通过消耗干细胞样癌细胞来阻断脑肿瘤异种移植物的形成和生长，但这类化合物具有显著的毒性。因此，我们计划研究ZSP是否可能通过阻断Notch活性来代表一种更有效和/或毒性更小的恶性脑肿瘤治疗方法。项目简介：本提案的目的是确定是否可以使用一种被称为禅生平（ZSP）的中草药治疗恶性脑肿瘤。最近发现ZSP抑制了癌细胞中一个重要的分子通路，即Notch。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（髓母细胞瘤）和成人（胶质母细胞瘤）中最常见的恶性脑肿瘤。