Murine Models for Studying Human Colon Cancer

描述（由申请人提供）：结直肠癌是美国癌症死亡的第二大原因。1995年，约有16万结直肠癌新病例，其中6万人死于该疾病。在了解病因和改善这种疾病的治疗方面取得进展的要求之一是发展新的动物模型，在这些模型中可以研究正常组织生物学和癌变的所有阶段。这些工具已经到位，可以为癌症研究准备新的小鼠模型；我们需要的是基础研究人员和临床研究人员之间就人类肿瘤的分子生物学、它们的起源和进展以及小鼠和大鼠的生物学相关性和模型进行持续的对话。为此，本申请中提出的会议将于2010年10月19日至22日在缅因州巴尔港的杰克逊实验室举行。我们没有安排一系列讲座，而是设计这次会议，在半天的会议中讨论六组当前问题：1)易感性/抗性遗传因素和GWAS， 2)干细胞和祖细胞；(聚)单克隆;3)基因组稳定性（CIN和MIN）和表观遗传因子（CIMP）：多途径假说；体细胞突变和增殖；诊断和预后的生物标志物；锯齿状、鳞状和直肠肿瘤；纵向研究；4)发育不良；EMT;极性;(a)细胞对称分裂；5)炎症和环境危险因素；肠道菌群;化学预防；6)早期发现；治疗的目标。每届会议将由一名现任报告员主持。我们打算在上午（9 - 12:30）和下午（2:30 - 6:00）安排半天的课程，各有30分钟的休息时间。每次会议通常有两个20分钟的演讲和六个10分钟的演讲，每次演讲后有5分钟的讨论时间。报告员将在每届半天会议开始时作10分钟的介绍，并在会议结束时主持10分钟的一般性讨论。我们相信，结肠癌的研究领域正在达到一个激动人心的时刻，值得举办一个包括高级和初级研究人员在内的互动会议。此外，Bar Harbor的环境将为这类会议提供一个可以蓬勃发展的场所，这与城市环境中的大型会议形成鲜明对比，在城市环境中，演讲者进行演讲，然后只与预先确定的同事会面。

DESCRIPTION (provided by applicant): Colorectal cancer is the second leading cause of cancer deaths in the United States. In 1995, there were about 160,000 new cases of colorectal cancers with 60,000 deaths resulting from the disease. One of the requirements for progress in understanding the etiology and improving the treatment of this disease is the development of new animal models in which normal tissue biology and all stages of carcinogenesis can be investigated. The tools are in place to prepare new mouse models for cancer research; what is needed is a continuing dialog between basic and clinical researchers about the molecular biology of human tumors, their initiation and progression with respect to biological correlates and modeling in mice and rats. To this end, the meeting proposed in this application will be hosted by The Jackson Laboratory in Bar Harbor Maine on October 19-22, 2010. Rather than scheduling a series of lectures, we are designing this conference to address six sets of current issues in half-day sessions: 1) Susceptibility/resistance genetic factors and GWAS, 2) Stem and progenitor cells; (poly)clonality; culturing crypts and epithelia, 3) Genomic (in)stability (CIN and MIN) and epigenetic factors (CIMP): The multiple pathway hypothesis; somatic mutations and epimutations; biomarkers for diagnosis and prognosis; serrated, squamous, and rectal tumors; longitudinal studies, 4) Dysplasia; EMT; polarity; (a)symmetric cell division; progression, 5) Inflammation and environmental risk factors; intestinal flora; chemoprevention, and 6) Early detection; therapeutic targets. Each Session will be chaired by an active Rapporteur. We intend to schedule the half-day sessions for morning (9 - 12:30) and afternoon (2:30 - 6:00), each with a 30- minute break. Each session will typically have two 20-minute talks and six 10-minute talks, with five minutes for discussion after each talk. The Rapporteur will provide 10 minutes of introduction at the beginning and lead 10 minutes of general discussion at the end of each half-day session. We believe that the field of research on colon cancer is reaching an exciting point, one that deserves an interactive conference involving both senior and junior investigators. Furthermore, the setting in Bar Harbor will provide a venue in which this sort of conference can thrive, in contrast to larger conferences in urban settings where speakers give lectures and then meet only with pre-determined colleagues. PUBLIC HEALTH RELEVANCE: Colon cancer remains one of the leading health threats in the U.S. today. In order to realize the development of effective models of human cancer, it is critical that basic and clinical researchers maintain clear lines of communication that promote a complete bilateral understanding of the disease and its phenotypes in animal models and how this translates to the study and treatment of the human disease. )