SPORE IN LUNG CANCER

肺癌中的孢子

• 批准号: 6651434
• 负责人: PAUL A. BUNN
• 金额: $ 306.85万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6651434
• 关键词: lung neoplasms

This University of Colorado Cancer Center proposes to continue its Specialized Program of Research Excellence (SPORE) in Lung Cancer to expand our understanding of the biology of lung cancer, to find new methods of diagnosis, prevention and treatment and to serve as a regional, national and international resource for the study of lung cancer. During the initial 2 1/2 years of our SPORE program, we were able to translate many basic science observations into relevant clinical studies. With respect to early detection, we: 1) collected more than 900 sputum samples from high- risk individuals and shoed that 27% of these had moderate dysplasia ro higher grade change and have accessioned these patients for continued observation; 2) accessioned more than 200 lung cancer specimens of all histologic types with matching pre and post surgical sputum samples for genetic testing of genes on chromosome 3p, 9p, 11q, and 17p; 3) showed that 3p genetic losses are among the first to occur in dysplasia; 4) developed FISH probes for evaluating 3p changes; 5) showed that pulmonary peptide production is an indicator of susceptibility to lung cancer, 6) showed that a fluorescent bronchoscope can detect regions of dysplasia in the bronchial epithelium, and 7) established a familial lung cancer clinic. With respect to prevention, we: 1) instituted a randomized study to determine the effects of chemoprevention (retinoids and alpha tocopherol) on intermediate endpoints in the respiratory epithelium; 2) instituted smoking cessation study; and 3) developed new secondary prevention strategies showing that: a) NEP expression is low or absent in lung cancer and that recombinant NEP therapy inhibits lung cancer growth, b) cyclin D1 is overexpressed in new small cell lung cancer while RB is absent in SCLC and that anti-sense cyclin D1 can reverse cyclin D1 overexpression and inhibit growth; c) certain pharmacologic agents (e.g., substance P derivatives and bradykinin analogs) and mutant genes (e.g., Galpha16Q212L) induce discordant signalling in SCLC cells leading to apoptosis through activation of the JNK pathway; and d) developed intratracheal and aerosolized inhalation delivery techniques. With respect to the development of new treatment strategies, the above statements on developing prevention strategies apply and se; 1) completed a phase I study of dexnigulidipine which determined the dose for phase II studies and are nearing completion of the phase II study; 2) accrued over 100 patients to phase I studies of new therapies in advanced lung cancer showing the MTD for paclitaxel/carboplatin in NSCLC and paclitaxel/etoposide/cisplatin in SCLC demonstrating that these are among the most active regimens known. During the next 5 years, we will expand on the discoveries to date by; 1) conducting 8 inter-relating full research projects (5 continuing, 3 new); 2) initiating 4--5 pilot projects annually; 3) conducting more than 12 clinical trial; 4) supporting 5 core resources including the expanded premalignant and cancer bank; 5) supporting the career development of 2 or 3 individuals annually; and 6) supporting t he recruitment of new areas of expertise in the study of lung cancer. The materials collected in our tissue banks will continue to be made available to scientists worldwide. We will continue our collaborations with other lung cancer SPORE and lung cancer scientists to reach our goals.

这个科罗拉多大学癌症中心建议继续 肺癌的专业研究卓越研究计划（Spore）扩展 我们对肺癌生物学的理解，以找到 诊断，预防和治疗，并充当区域性的国家 和肺癌研究的国际资源。 在 最初的2 1/2年的孢子计划，我们能够翻译许多 基础科学观察到相关的临床研究。 关于 早期检测，我们：1）从高级收集了900多个痰液样品 风险个人，并剥夺其中27％的发育不良RO 高年级变化，并为这些患者加入了 观察； 2）登录所有的200多个肺癌标本 具有匹配前后手术痰样品的组织学类型的类型 基因3p，9p，11q和17p上基因的基因测试； 3）表明 3p遗传损失是发育不良中最早发生的； 4）开发 用于评估3P变化的鱼类探针； 5）表明肺肽 生产是对肺癌易感性的指标，6）表明 荧光支气管镜可以检测支气管中发育不良的区域 上皮和7）建立了家族性肺癌诊所。 尊重 为了预防，我们：1）进行了一项随机研究，以确定 化学预防（类视黄醇和α生育酚）对中级的影响 呼吸上皮中的终点； 2）戒烟 学习; 3）制定了新的二级预防策略，表明： a）NEP表达低或在肺癌中不存在，并且重组NEP 治疗抑制肺癌的生长，b）细胞周期蛋白D1在新的 小细胞肺癌，而RB在SCLC中不存在，并且反态 细胞周期蛋白D1可以逆转Cyclin D1过表达并抑制生长。 c） 某些药理学剂（例如，物质P衍生物和心动激肽 类似物）和突变基因（例如Galpha16Q212L）诱导不一致 通过激活JNK，SCLC细胞中的信号传导导致凋亡 途径； d）发出了气管内和雾化的吸入输送 技术。 关于制定新的治疗策略， 上述有关制定预防策略的声明适用和SE； 1） 完成了右旋吡啶的I期研究，该研究确定了 第二阶段研究，即将完成II期研究； 2） 收取100多名患者，对先进的新疗法进行I期研究 肺癌显示了NSCLC和 SCLC中的紫杉醇/依托泊苷/顺铂证明了这些 最活跃的方案已知。 在接下来的5年中，我们将扩展 约会的发现； 1）进行8个相互关联的完整研究 项目（5个继续，3个新的）； 2）每年启动4--5个试点项目； 3）进行12次以上的临床试验； 4）支持5个核心资源 包括扩大的预立式和癌症银行； 5）支持 每年2或3个人的职业发展； 6）支持他 招募肺癌研究的新专业知识领域。 这 将继续提供在我们组织库中收集的材料 给全球科学家。 我们将继续与其他 肺癌孢子和肺癌科学家实现我们的目标。