Tumor Biology & Progression

8.4.1摘要：肿瘤生物学与进展， 肿瘤生物学和进展计划由詹姆斯·麦卡锡博士领导，有27名成员，包括： 代表16个部门和5所学校。截至2007年10月1日，这些会员总共拥有6.5美元 在本预算期内，由同行评审、资助的研究项目达100万个。自2003年6月以来，他们的 研究产生了172份出版物，其中14%是方案内出版物，15%是方案间出版物。 肿瘤生物学和进展计划中的研究重点是分子和 与恶性肿瘤进展相关的细胞机制。该计划有三个主要方面 科学焦点领域或主题。首先，项目成员正在研究肿瘤生长/存活的生物学 以及评价肿瘤微环境在进展中的重要贡献。热休克的作用 蛋白70在胰腺癌细胞耐药中的作用及特异性抑制物的筛选 正在寻求改进治疗方法。使用新辅助疗法治疗胰腺癌的新方案是 正在开发并在该疾病的原位动物模型中进行测试。新入职教职员工正在学习 巨噬细胞在转基因动物早期进展相关事件中的重要性 乳腺癌的模型。研究也在进行中，以检验明确的抗血管生成的作用机制。 药物，包括新型工程非肽模拟血管生成抑制剂。第二，那里 是一个由临床研究人员和基础科学家组成的前列腺癌焦点小组。 研究包括确定雄激素受体如何调节激素难治性疾病的生长， 细胞内的激酶如CK2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，以评估交付RNA的可行性 使用亚50纳米纳米胶囊的基于干扰的治疗。破坏透明质酸/的合成肽 肿瘤细胞的相互作用在体外和体内都在评估限制肿瘤生长的能力。 前列腺癌分期的非侵入性成像方法的发展及其与 人们也在寻求更传统的分子进展相关性。最后，新型免疫毒素 正在开发以改进对各种造血和实体组织肿瘤的治疗。这些 研究涉及设计双价SFV抗体与白喉毒素相结合，以靶向和杀死肿瘤： 其中一些药物目前处于I期临床试验，其他药物正在开发中，用于未来的临床 学习。该计划的长期目标是识别和定位恶性肿瘤使用的关键途径 治疗生长失调、侵袭和抵抗治疗的药物。

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.