Tumor Biology & Progression

肿瘤生物学

• 批准号: 7944859
• 负责人: James B. McCarthy
• 金额: $ 2.61万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-08 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7944859
• 关键词: Androgen Receptor; Angiogenesis Inhibitors; Animal Disease Models; Animal Model; Antibodies; Area; Biology; Budgets; Cancer Center Support Grant; Cell Adhesion; Cell Communication; Clinical Research; Coupled; Development; Doctor of Philosophy; Engineering; Event; Faculty; Focus Groups; Funding; Future; Goals; Growth; Heat-Shock Proteins 70; Hematopoietic; Hyaluronan; Image; Immunotoxins; In Vitro; Infiltration; Investigation; Malignant Neoplasms; Malignant neoplasm of pancreas; Malignant neoplasm of prostate; Molecular; Names; Neoadjuvant Therapy; Neoplasm Metastasis; Neoplasms; Pathway interactions; Peer Review; Phase I Clinical Trials; Phosphotransferases; Prostatic Neoplasms; Protocols documentation; Publications; RNA Interference; Refractory Disease; Research; Research Personnel; Research Project Grants; Resistance; Role; Schools; Solid; Somatotropin; Staging; Testing; Therapeutic; Toxin; Transgenic Animals; Translational Research; Tumor Biology; Tumor Cell Invasion; Tumor Tissue; abstracting; base; cancer cell; design; improved; in vivo; inhibitor/antagonist; interest; killings; macrophage; malignant breast neoplasm; member; mimetics; neoplastic cell; new therapeutic target; novel; programs; synthetic peptide; therapy resistant; tumor; tumor growth; tumor progression

8.4.1 ABSTRACT: TUMOR BIOLOGY AND PROGRESSION, The Tumor Biology and Progression program, led by James McCarthy, Ph.D., has 27 members, : representing 16 departments and five schools. As of October 1, 2007, these members have a total of $6.5 million in peer-reviewed, funded research projects for the current budget period. Since June 2003, their research has resulted in 172 publications, of which 14% were intra-programmatic and 15% were interprogrammatic. Research within the Tumor Biology and Progression Program focuses on molecular and cellular mechanisms associated with the progression of malignant tumors. The program has three major scientific focus areas or themes. First, program members are studying the biology of tumor growth/survival and evaluating important contributions of the tumor microenvironment in progression. The role of heat shock protein 70 in the therapeutic resistance of pancreatic cancer cells and identification of specific inhibitors to improve therapy are being pursued. New protocols using neoadjuvant therapies for pancreatic cancer are being developed and tested in orthotopic animal models of the disease. Newly recrujted faculty are studying the importance of macrophage infiltration to early progression associated events in a transgenic animal model of breast cancer. Studies are also in progress to examine mechanisms of action Of defined antiangiogenic agents, including novel engineered nonpeptide mimetic inhibitors of angiogenesis. Second, there is a prostate cancer focus group that consists of clinincal investigators and basic scientists.Projects being pursued include determining how androgen receptors regulate the growth of hormone refractory disease, how intracellular kinases such as CK2 confer survival, and how hyaluronan within the microenvironment facilitates progression. These studies are being extended to evaluate feasibility of delivering RNA interference based therapies using sub 50nm nanocapsules. Synthetic peptides that disrupt hyaluronan/ tumor cell interactions are being evaluated in vitro and in vivo for the ability to limit tumor growth. Development of noninvasive imaging approaches for staging prostate tumors and relating these results to more conventional molecular correlates of progression is also being pursued. Finally, novel immunotoxins are being developed to improve the treatment of various hematopoietic and solid tissue tumors. These studies involve the design of bivalent sFv antibodies coupled with diptheria toxin to target and kill neoplasms: Some of these agents are currently in phase I clinical trials and others are being developed for future clinical studies. The long term goal of the program is to identify and target key pathways used by malignant tumors for dysregulated growth, invasion and resistance to therapy.

8.4.1 摘要：肿瘤生物学和进展， 由 James McCarthy 博士领导的肿瘤生物学和进展项目有 27 名成员： 代表16个院系和5所学校。截至 2007 年 10 月 1 日，这些会员总共拥有 6.5 美元 当前预算期间的同行评审资助研究项目为 100 万美元。自 2003 年 6 月以来，他们 研究已发表 172 篇出版物，其中 14% 为计划内出版物，15% 为计划间出版物。 肿瘤生物学和进展计划的研究重点是分子和 与恶性肿瘤进展相关的细胞机制。该计划主要有三个 科学重点领域或主题。首先，项目成员正在研究肿瘤生长/存活的生物学 并评估肿瘤微环境在进展中的重要贡献。热激的作用 蛋白质70在胰腺癌细胞治疗耐药中的作用及其特异性抑制剂的鉴定 正在寻求改善治疗。使用新辅助疗法治疗胰腺癌的新方案是 正在该疾病的原位动物模型中进行开发和测试。新聘教师正在学习 巨噬细胞浸润对转基因动物早期进展相关事件的重要性 乳腺癌模型。研究也在进行中，以检查确定的抗血管生成的作用机制 药物，包括新型工程化的血管生成非肽模拟抑制剂。其次，有 是一个前列腺癌焦点小组，由临床研究人员和基础科学家组成。项目包括 追求的目标包括确定雄激素受体如何调节激素难治性疾病的生长， CK2 等细胞内激酶如何赋予生存，以及微环境中的透明质酸如何 促进进步。这些研究正在扩展以评估递送 RNA 的可行性 使用亚 50 纳米纳米胶囊的基于干扰的疗法。破坏透明质酸的合成肽/ 正在体外和体内评估肿瘤细胞相互作用限制肿瘤生长的能力。 开发用于对前列腺肿瘤进行分期并将这些结果与 更传统的进展分子相关性也在探索中。最后，新型免疫毒素 正在开发用于改善各种造血系统和实体组织肿瘤的治疗。这些 研究涉及设计与白喉毒素结合的二价 sFv 抗体来靶向并杀死肿瘤： 其中一些药物目前正处于 I 期临床试验，其他药物正在开发用于未来的临床 研究。该计划的长期目标是识别和靶向恶性肿瘤使用的关键途径 用于生长失调、侵袭和对治疗的抵抗。