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“以患者为导向的研究中的中级研究者奖：PA-00-005”题为造血性疾病的治疗策略。 血细胞的形成代表了干细胞，构成基质微环境和生长调节蛋白的天花板之间的复杂相互作用，这些蛋白质以可溶性和局部形式呈现。 这些相互作用引起了巨大的细胞数量和多样性，这些细胞在人体广泛分离的部分运输氧气，防御感染剂并提供凝结的刺激。 损害血细胞发育过程的异常，例如骨髓增生和急性骨髓性白血病（AML）；除癌症外，还可以导致威胁生命的疾病，例如谱系特定的骨髓抑制或全细胞减少症，从而产生明显的发病率和死亡率。 该提案着重于基于科学的假设驱动的试点临床研究的发展，行为和指导，旨在利用这些特定疾病的固有生物学特征。 候选人目前（目前由K24支持）的三个不同的中央假设是临床研究工作的基础：1）分别在AML和MDS中干扰或反转录抑制的药物的治疗应用将分别具有临床效用； 2）抑制自分泌和微环境提出的生长因子，这有助于延迟程序性细胞死亡，这是诸如慢性淋巴细胞性白血病（CLL）等疾病的特征，代表了一种潜在效用的新型治疗方法； 3）细胞因子抑制红细胞生成的抑制作用会导致癌症的贫血；克服细胞因子抑制作用的策略应增加癌症患者的红细胞产生，并进一步减少该人群中贫血的临床问题。 该应用程序的重要组成部分是对主要的初级教师和血液学/肿瘤学研究员的积极指导，他们选择从事学术临床研究作为职业道路。 该指导计划包括：1）与NIH资助的临床研究培训计划（K30）一起参加特定课程，候选人担任首席研究员和IRB临床研究行为课程； 2）直接监督，包括：（a）协议和IND开发的每周会议； （b）应计数据和监管审查； （c）手稿和演示准备。