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Intermediate endpoint biomarkers for lung cancer chemoprevention

机译:肺癌化学预防的中间终点生物标志物

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Abstract: Given the demographics of current and ex-smoking populations in North America, lung cancer will be a major problem in the foreseeable future. Early detection and treatment of lung cancer holds great promise for the management of this disease. Unlike cervical cancer, the physical, complete removal/destruction of all dysplastic lesions in the bronchial tree is not possible; however, treatment of the lesions using a chemopreventive agent is. Intermediate biomarkers have been used to screen promising chemopreventive agents for larger population studies. We have examined the natural history of lung cancer development by following a group of subjects at high risk of developing lung cancer using fluorescence endoscopy to identify the areas of abnormality for biopsy. Approximately 900 biopsies have been collected in this fashion and graded by at least two experienced, expert pathologists. Using an interactive version of the Cyto-Savant (Oncometrics Imaging Corp.), cytometric and tissue architectural data were collected from these biopsies. Using only the data from the normal and invasive cancer biopsies, quantitative morphometric and architectural indices were generated and calculated for all the collected biopsies. These indices were compared with Loss of Heterozygosity (LOH) of ten sites commonly associated with cancer. These results and the application of these quantitative measures to two small chemoprevention studies will be reported. !19
机译:摘要:鉴于北美当前和吸烟人群的人口统计资料,在可预见的将来,肺癌将成为主要问题。肺癌的早期发现和治疗对该疾病的治疗具有广阔的前景。与宫颈癌不同,不可能完全清除/破坏支气管树中所有增生性病变;然而,使用化学预防剂治疗病变是可以的。中间生物标志物已被用于筛选有前途的化学预防剂,以用于更大的人群研究。通过使用荧光内窥镜检查确定一组活检异常区域,我们追踪了一组罹患肺癌的高风险人群,从而检查了肺癌发展的自然史。以此方式收集了大约900份活检样本,并由至少两名经验丰富的专业病理学家进行了分级。使用Cyto-Savant(Oncometrics Imaging Corp.)的交互式版本,从这些活检样本中收集了细胞计数和组织结构数据。仅使用来自正常和浸润性癌症活检的数据,就所有收集到的活检生成并计算了定量形态和建筑指标。将这些指数与通常与癌症相关的十个位点的杂合性丧失(LOH)进行了比较。将报告这些结果以及这些定量方法在两项小型化学预防研究中的应用。 !19

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