Biomathematical Approaches to Cancer

癌症的生物数学方法

• 批准号: 6771083
• 负责人: SURESH H MOOLGAVKAR
• 金额: $ 21.63万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6771083
• 关键词: Barretts esophagus; adenocarcinoma; apoptosis; carcinogenesis; cell cycle; cell proliferation; clinical research; colon neoplasms; computer data analysis; human data; laboratory rat; liver neoplasms; mathematical model; mathematics; morphology; preneoplastic state; statistics /biometry

DESCRIPTION (provided by applicant): Clones of intermediate cells on the pathway to cancer, such as adenomatous polyps and altered hepatic foci, are often observed in humans and animals. These lesions provide insights into the earliest stages of the carcinogenic process. Because clonal expansion of cells that are partially transformed can increase the probability of cancer substantially, a quantitative understanding of these lesions is key to understanding cancer rates. The broad objective of this project is to continue the development of mathematical, statistical and computational tools, within the paradigm of multistage carcinogenesis, for the quantitative analyses of early lesions on the pathway to malignancy. The fundamental goals of these analyses are to study the temporal evolution of these lesions, to estimate the rate of initiation of the lesions, and the rates of cell division and apoptosis of the partially transformed cells that comprise the lesion. Information on such early lesions is typically available from initiation-promotion experiments, particularly in the rodent liver.In previous work mathematical expressions have been developed for the number and size distribution of intermediate lesions on the pathway to malignancy and used for analyses of initiation-promotion experiments in rat liver. This proposal plans to extend this work in light of new biological information. In addition to continuing work on analyses of liver foci in rodents, the research proposed here will investigate intermediate lesions in the human colon and in patients with Barrett's esophagus, a high-risk precursor condition for adenocarcinoma of the esophagus. In addition to the mathematical and statistical problems associated with clonal growth models within the paradigm of multistage carcinogenesis, both analyses of liver foci and analyses of lesions in Barrett's esophagus present diverse problems. Recognizing that modeling is an iterative process an integral part of this effort will be collaboration with experimentalists and human biologists, in particular Dr. Michael Schwarz, University of Tubingen, an expert on the rodent liver system, Dr. John Potter, an epidemiologist with expertise on colon cancer and Dr. Brian Reid, Director of the Seattle Barrett's Esophagus Project. The results of analyses will be used to help generate biologically relevant questions and hypotheses and to plan further experiments and studies, which, in turn, will lead to more refined models.

描述（由申请人提供）：在人类和动物中经常观察到癌症途径中的中间细胞克隆，例如腺瘤性息肉和改变的肝病灶。这些病变让我们了解致癌过程的最早阶段。由于部分转化的细胞的克隆扩增会大大增加患癌症的可能性，因此对这些病变的定量了解是了解癌症发生率的关键。该项目的总体目标是在多阶段癌发生的范式内继续开发数学、统计和计算工具，用于对恶性肿瘤途径中的早期病变进行定量分析。这些分析的基本目标是研究这些病变的时间演变，估计病变的发生率，以及构成病变的部分转化细胞的细胞分裂和凋亡率。有关此类早期病变的信息通常可以从启动促进实验中获得，特别是在啮齿动物肝脏中。在之前的工作中，已经开发了针对恶性肿瘤途径中中间病变的数量和大小分布的数学表达式，并用于分析大鼠肝脏中的启动促进实验。该提案计划根据新的生物信息扩展这项工作。除了继续对啮齿动物肝脏病灶进行分析之外，这里提出的研究还将调查人类结肠和巴雷特食管患者的中间病变，巴雷特食管是食管腺癌的高风险先兆病症。除了与多阶段癌发生范式内的克隆生长模型相关的数学和统计问题之外，对肝病灶的分析和对巴雷特食管病变的分析都存在不同的问题。认识到建模是一个迭代过程，这项工作的一个组成部分将是与实验学家和人类生物学家的合作，特别是图宾根大学啮齿动物肝脏系统专家 Michael Schwarz 博士、结肠癌专业流行病学家 John Potter 博士和西雅图巴雷特食管项目主任 Brian Reid 博士。分析结果将用于帮助产生生物学相关的问题和假设，并计划进一步的实验和研究，这反过来又将产生更完善的模型。