MITOSIN A NEW PROLIFERATION MARKER FOR CANCER DIAGNOSIS

核分裂素是癌症诊断的新增殖标志物

• 批准号: 2869847
• 负责人: ROBERT J CHRISTY
• 金额: $ 10.01万
• 依托单位: GENETEX, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-13 至 1999-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2869847
• 关键词: biomarker; breast neoplasm /cancer diagnosis; cell cycle; cell proliferation; diagnosis design /evaluation; diagnostic tests; flow cytometry; immunocytochemistry; immunofluorescence technique; immunoprecipitation; laboratory mouse; monoclonal antibody; phosphoproteins; prognosis; western blottings

Diagnosis of breast cancer presents several dilemmas for patients and clinicians such as whether or not to use systemic adjuvant therapy following surgery. Management of such patients would be optimized if clinicians had a molecular fingerprint of a patient's tumor at the time of diagnosis that would accurately predict recurrence and treatment responses. As such, cell proliferation has been used as a mitotic index to monitor disease status in histologic grading systems; however, this approach is tedious to perform. Newer methods such as DNA flow cytometry have been used to correlate S-phase fraction of cells with clinical outcomes of patients with primary breast cancer. The expense of flow cytometry equipment, universal standardization of techniques and questions about reproducibility of results has limited its acceptance as a standard prognostic factor in the clinic. Recently, it has been shown that mitosin, a 350-kDa nuclear phosphoprotein, is specifically involved in mitotic phase progression. Preliminary results demonstrate that mitosin staining by immunohistochemistry is directly related to S-phase fraction and associated with early disease recurrence. In order to study the value of mitosin as a prognostic indicator we will develop monoclonal antibodies suitable for immunohistochemical staining of mitosin. These studies will provide the basic understanding of the prognostic significance of mitosin, in clinical samples that will lead to development of diagnostic test and treatment of human breast cancer. PROPOSED COMMERCIAL APPLICATIONS: Development of clinically useful monoclonal antibodies suitable for immunohistochemical staining of mitosin which will serve to replace expensive and tedious flow cytometry analysis of S-phase fraction as a prognostic factor for primary breast cancer. We will develop antibodies that will work and give consistent results under a wide variety of fixation procedures and staining techniques. This will lead to development of a simple, inexpensive diagnostic test, which will be available to breast cancer patients in smaller, non-academic treatment centers.

乳腺癌的诊断给患者和临床医生带来了一些困境，例如手术后是否使用全身辅助治疗。如果临床医生在诊断时掌握了患者肿瘤的分子指纹，可以准确预测复发和治疗反应，那么对此类患者的管理将会得到优化。因此，细胞增殖已被用作有丝分裂指数来监测组织学分级系统中的疾病状态；然而，这种方法执行起来很乏味。 DNA 流式细胞术等较新的方法已用于将细胞的 S 期分数与原发性乳腺癌患者的临床结果相关联。流式细胞术设备的费用、技术的普遍标准化以及结果再现性的问题限制了其作为临床标准预后因素的接受度。最近，研究表明核分裂素（一种 350 kDa 的核磷蛋白）专门参与有丝分裂期的进展。 初步结果表明，免疫组织化学的核分裂激素染色与 S 期分数直接相关，并与早期疾病复发相关。为了研究核分裂激素作为预后指标的价值，我们将开发适合核分裂激素免疫组织化学染色的单克隆抗体。 这些研究将提供对临床样本中核分裂激素的预后意义的基本了解，从而促进人类乳腺癌诊断测试和治疗的发展。拟议的商业应用：开发适用于核分裂激素免疫组织化学染色的临床有用的单克隆抗体，这将取代昂贵且繁琐的 S 期部分流式细胞术分析作为原发性乳腺癌的预后因素。我们将开发能够在各种固定程序和染色技术下发挥作用并提供一致结果的抗体。这将导致一种简单、廉价的诊断测试的开发，该测试将可供较小的非学术治疗中心的乳腺癌患者使用。