BP1 and Nuclear Hormone Signaling in Breast Cancer

乳腺癌中的 BP1 和核激素信号传导

• 批准号: 7124622
• 负责人: JANICE L GABRILOVE
• 金额: $ 13.59万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-23 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7124622
• 关键词: acute myelogenous leukemia; apoptosis; autocrine; blood disorder chemotherapy; cell differentiation; chronic lymphocytic leukemia; clinical research; clinical trial phase I; clinical trial phase II; dyserythropoietic anemia; erythropoiesis; erythropoietin; gene induction /repression; hematopoiesis; human subject; human therapy evaluation; patient oriented research; tumor necrosis factor alpha

DESCRIPTION (provided by applicant): This is a "Midcareer Investigator Award in Patient-Oriented Research: PA-00-005" entitled Therapeutic Strategies in Disorders of Hematopoiesis. The formation of blood cells represents a complex interaction between stem cells, ceils making up the stromal microenvironment and growth regulatory proteins, which are presented in soluble and localized forms. These interactions give rise to an enormous number and diversity of cells that function in widely separated parts of the body to transport oxygen, defend against infectious agents and provide stimulus for clotting. Abnormalities that impair the process of blood cell development, such as Myelodysplasia and Acute Myelogenous Leukemia (AML); as well as Cancer, can lead to life threatening illness as welt as lineage specific myelosuppression or pancytopenia resulting in significant morbidity and mortality. This proposal focuses on the development, conduct and mentoring of scientifically based, hypothesis-driven pilot clinical investigations, designed to exploit inherent biological features of these specific diseases. Three distinct central hypotheses underlie the Candidate's present (currently funded) and new (to be supported by K24) clinical research efforts: 1) the therapeutic application of agents that interfere or reverse transcriptional repression will be of clinical utility in AML and MDS respectively; 2) inhibition of autocrine and microenvironmentally presented growth factors, which contribute to delays in programmed cell death, characteristic of disorders such as chronic lymphocytic leukemia (CLL), represents a novel therapeutic approach of potential utility; and 3) cytokines inhibitory for erythropoiesis contribute to anemia of cancer; strategies to overcome cytokine inhibition should augment red blood cell production in cancer patients and further reduce the clinical problem of anemia in this population. An important part of this application concerns the active mentorship of key junior faculty and hematology/oncology fellows who have chosen to pursue academic clinical research as a career path. This mentorship program consists of: 1) participation in specific curriculum in conjunction with the NIH funded Clinical Research Training Program (K30), for which the candidate serves as the Principal investigator, and IRB course on conduct in Clinical Research; 2) direct oversight, including weekly meetings for: (a) protocol and IND development; (b) accrual, data and regulatory review; (c) manuscript and presentation preparation.

描述（由申请人提供）：这是一个“以患者为导向的研究中期研究者奖：PA-00-005”，题为造血功能障碍的治疗策略。 血细胞的形成代表了干细胞、构成基质微环境的细胞和以可溶性和局部形式存在的生长调节蛋白之间的复杂相互作用。 这些相互作用产生了大量和多样性的细胞，这些细胞在身体的广泛分离的部位发挥作用，以运输氧气，抵御感染因子并为凝血提供刺激。 损害血细胞发育过程的疾病，如骨髓增生异常和急性骨髓性白血病（AML）;以及癌症，可导致危及生命的疾病以及谱系特异性骨髓抑制或全血细胞减少，导致显著的发病率和死亡率。 该提案侧重于开发、开展和指导以科学为基础、以假设为驱动的试点临床研究，旨在利用这些特定疾病的固有生物学特征。 三个不同的中心假设构成了候选人的现状（目前供资）和新设（将由K24支持）临床研究工作：1）干扰或逆转录抑制剂的治疗应用将分别在AML和MDS中具有临床效用; 2）抑制自分泌和微环境呈递的生长因子，其有助于延迟程序性细胞死亡，细胞因子抑制是疾病如慢性淋巴细胞白血病（CLL）的特征，代表了具有潜在效用的新的治疗方法;和3）抑制红细胞生成的细胞因子导致癌症贫血;克服细胞因子抑制的策略应该增加癌症患者中的红细胞产生，并进一步减少该群体中贫血的临床问题。 该申请的一个重要部分是对选择从事学术临床研究作为职业道路的主要初级教师和血液学/肿瘤学研究员的积极指导。该指导计划包括：1）参与特定课程与NIH资助的临床研究培训计划（K30），其中候选人担任首席研究员，和IRB关于临床研究行为的课程; 2）直接监督，包括每周会议：（a）方案和IND开发;（B）应计、数据和监管审查;（c）手稿和演示文稿准备。