HEMATOPOIETIC PROGENITOR CELLS

描述：(申请者摘要)大剂量自体化疗 造血祖细胞支持是治疗选择性白血病的有效方法 高危乳腺癌患者。这方面的主要限制 治疗策略包括1)潜在的乳腺癌细胞污染 自体造血细胞移植；2)诱导的骨髓抑制 发病率和死亡率；以及3)#年乳腺癌根除不彻底。 大多数患者为IV期疾病。申请人姓名的首字母 格兰特开始通过进行临床研究来解决这些局限性。 造血祖细胞纯化方法的评价。此次续订 应用程序将通过追求几个不同的方式继续走上这条道路 战略。目标1将继续专注于开发和临床 乳腺癌细胞脱除最佳方法的评价 自体移植。目标2旨在提高检测乳房的能力 自体移植物中的癌细胞，特别是那些具有克隆性的癌细胞 潜力，并评估它们对移植后疾病复发的影响。 目标3将评估造血细胞作为乳房的体外扩增 癌症净化策略及其作为缩短大剂量给药周期的方法 同种异体移植环境中治疗引起的骨髓抑制。目标 4的目的是开发一种临床相关的小鼠试验 潜在地预测操控造血祖细胞的性能 在申请人的病人身上。临床前研究人员生成的数据 调查和拟议的临床研究将使她能够设计 治疗预后不良妇女的更有效策略 乳腺癌。该应用程序的创新方面包括使用 将体外扩增作为一种清除策略来根除乳腺癌 自体移植和扩大的异基因脐带血支持治疗 不适合进行自体移植的患者。都不是 战略之前已经使用过，而且两者都有可能 大幅改善乳腺癌患者的临床结局。 申请者的小组在过渡研究方面有经过证明的记录 造血细胞支持的乳房治疗领域的生产力 癌症患者，并很有可能回答这些问题 在此续期申请中提出。

DESCRIPTION: (Applicant's Abstract) High-dose chemotherapy with autologous hematopoietic progenitor cell support is effective treatment for selected patients with high-risk breast cancer. Major limitations of this therapeutic strategy include 1) potential breast cancer cell contamination of the autologous hematopoietic cell grafts; 2) myelosuppression induced morbidity and mortality; and 3) incomplete eradication of breast cancer in the majority of patients with stage IV disease. The applicant's initial grant began to address these limitations by conducting clinical studies evaluating the purification of hematopoietic progenitor cells. This renewal application will continue on that path by pursuing several different strategies. Aim 1 will continue to focus on the development and clinical evaluation of optimal methods for removing breast cancer cells from the autografts. Aim 2 is directed at improving the ability to detect breast cancer cells in the autografts, particularly those with clonogenic potential, and assess their impact on post transplant relapse of disease. Aim 3 will evaluate the ex vivo expansion of hematopoietic cells as a breast cancer purging strategy and as a method to reduce the period of high-dose therapy-induced myelosuppression in the allogeneic transplant setting. Aim 4 is directed toward developing a clinically relevant mouse assay to potentially predict the performance of manipulated hematopoietic progenitors in the applicant's patients. The data generated by the preclinical investigations and the proposed clinical studies will enable her to devise the more efficacious strategies for treating women with poor prognosis breast cancer. The innovative aspects of this application include the use of ex-vivo expansion as a purging strategy to eradicate breast cancer from autografts and the use of expanded allogeneic cord blood support for patients who are not good candidates for autologous transplants. Neither strategy has been employed previously, and both have the potential to substantially improve the clinical outcome of patients with breast cancer. The applicant's group has a proven track-record of transitional research productivity in the area of hematopoietic cell supported therapy of breast cancer patients, and will very likely be able to answer the questions proposed in this renewal application.