HEMATOPOIETIC PROGENITOR CELLS

描述：（申请人的摘要）高剂量化疗与自体 造血祖细胞支持是选择性 高危乳腺癌患者。 主要局限性 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）骨髓抑制诱导 发病率和死亡率;和3）乳腺癌的不完全根除， 大多数患者为IV期疾病。 申请人姓名首字母 格兰特开始通过进行临床研究来解决这些局限性 评价造血祖细胞的纯化。 此续订 应用程序将继续在这条道路上追求几个不同的 战略布局 目标1将继续专注于开发和临床 评价从乳腺癌组织中去除乳腺癌细胞的最佳方法 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，特别是具有克隆形成的那些 潜力，并评估其对移植后疾病复发的影响。 目的3将评估造血细胞作为乳腺癌的体外扩增 癌症清除策略，并作为一种方法，以减少高剂量的时间 同种异体移植环境中治疗诱导的骨髓抑制。 目的 4涉及开发临床相关的小鼠测定， 有可能预测经操纵的造血祖细胞的表现 申请人的病人。 临床前研究生成的数据 调查和拟议的临床研究将使她能够设计 更有效的治疗预后不良的女性的策略 乳腺癌 该应用程序的创新方面包括使用 体外扩增作为根除乳腺癌的清除策略， 自体移植和使用扩增的同种异体脐带血支持， 不适合自体移植的患者。 既不 这两种战略都有可能， 显著改善乳腺癌患者的临床结果。 申请人的团队在过渡研究方面有着良好的记录 在造血细胞支持的乳腺癌治疗领域的生产力 癌症患者，并且很有可能能够回答这些问题， 在这次更新申请中。

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.