HPV ONCOPROTEIN EXPRESSION IN CERVICAL CANCER

描述：（申请人摘要）本项目的总体目标是 开发能够识别一部分患者的诊断检测方法 子宫颈发育不良的患者， 癌人乳头瘤病毒（HPV）16型E6或E7癌蛋白是主要的 宫颈癌的致病因子，并在高度异型增生中表达 宫颈病变和宫颈肿瘤组织。申请人的目标是 开发和评估E6和E7表达的检测方法， 来自有患宫颈癌风险的患者的组织。他会用这个 确定E6和E7癌基因表达是否与 与宫颈发育不良程度有关目前编码HPV的DNA 癌蛋白可用于诊断高危型HPV感染，但 HPV类型特异性DNA的存在并不提供关于是否 癌蛋白实际上是被表达出来的。申请人的数据 使用RT-PCR和RNA原位杂交的初步研究表明， E6和E7的表达可以在患有以下疾病的个体的组织中检测到： 宫颈发育不良和宫颈癌。他假设HPV 16 E6和E7 癌蛋白表达，使用HPV癌基因的诊断测定评估， 宫颈癌患者血液和组织中癌蛋白或其抗体 宫颈癌的发生与宫颈癌的分级有关。 发育不良或宫颈癌。为了验证这一假设，他提出了一个假设， 和E6融合蛋白，以开发用于检测E6和E7的新的诊断方法 RNA和癌基因在宫颈组织中的表达，并使用E6融合 蛋白质，以开发用于检测针对E6和E7的特异性抗体的测定法 宫颈癌患者血清中的癌蛋白。的 这些癌基因及其抗体的表达测定可用于 监测宫颈癌治疗方式的有效性，以及 将允许研究人员对患者进行干预， 上皮内瘤变，以减少未来发展的风险 侵袭性癌症

DESCRIPTION: (Applicant's Abstract) The overall objective of this project is to develop diagnostic assays that are capable of identifying a subset of patients with cervical dysplasia who are at increased risk of developing cervical cancer. Human papillomavirus (HPV) type 16 E6 or E7 oncoproteins are major causative agents in cervical cancer, and are expressed in high grade dysplastic lesions of the cervix and in cervical tumor tissue. The applicant's goal is to develop and evaluate assays of E6 and E7 expression that can be used to examine tissues from patients at risk for developing cervical cancer. He will use this information to determine whether E6 and E7 oncogene expression is associated with the grade of cervical dysplasia. At present the DNA that codes for HPV oncoproteins can be detected for diagnosis of high-risk HPV infection, but the presence of HPV type-specific DNA does not provide information about whether the oncoproteins are actually being expressed. Data from the applicant's preliminary studies using RT-PCR and RNA in situ hybridization demonstrated that E6 and E7 expression can be detected in the tissue of individuals with cervical dysplasia and cervical cancer. He hypothesizes that HPV 16 E6 and E7 oncoprotein expression, assessed using diagnostic assays of HPV oncogenes, oncoproteins or their antibodies in blood and tissues of patients with cervical dysplasia or cervical cancer will correlate with the grade of cervical dysplasia or cervical cancer. To test this hypothesis, he proposes to produce and E6 fusion protein, to develop new diagnostic assays for detecting E6 and E7 RNA and oncogene expression in cervical tissue, and to use the E6 fusion protein to develop assays for detecting antibodies specific against E6 and E7 oncoproteins in sera from patients at risk for developing cervical cancer. The assays of expression of these oncogenes and their antibodies can be used to monitor for the effectiveness of cervical cancer treatment modalities, and would allow investigators to make interventions in patients with intraepithelial neoplasia to decrease the risk of future development of invasive cancer.