ADENOVIRUS E1A AS A THERAPEUTIC AGENT IN BREAST CANCER

描述（申请人描述）： 职业目标：申请人的职业目标是成为一个既定的 在治疗领域的学术机构的医生-科学家， 涉及分子生物学技术在医学肿瘤学中的应用。 他 特别希望他能参与到乳腺癌的转化中来， 血液和骨髓剂量强化化疗相关研究 移植支持。 他坚信，理解 乳腺癌的分子机制将导致改善的长期， 晚期乳腺癌患者的无病生存率。 到 为了实现这一目标，他已经攻读了博士学位。在The University of 在米恩的监督下，德克萨斯州生物医学研究生院 Chie Hung博士作为一名工作人员， 德克萨斯大学血液和骨髓移植系。 D.安德森癌症中心。 建议：乳腺癌是最常见的癌症之一。 美国女性癌症死亡的常见原因。 主要 乳腺癌患者治疗失败的原因 剂量密集化疗仍然保持疾病复发，可能是由于 残留乳腺癌细胞的耐药性。 过表达 HER-2/neu癌基因发生在30%的乳腺癌中， 预后不佳。 这可能是由于HER-2/neu诱导了HER-2/neu的表达。 对化疗药物的耐药性。 腺病毒5型E1 A基因 已知产物在转录水平抑制HER-2/neu表达。 申办方的实验室先前已经证明HER-2/neu表达可以 在HER-2/neu过表达乳腺癌细胞系中被抑制， 腺病毒载体或阳离子脂质体作为E1 A的递送系统 基因 近年来，有研究表明E1 A基因可促进肿瘤的发生， 除了转录抑制外， HER-2/neu. 申请人目前正在进行I期临床试验 E1 A基因治疗HER-2/neu过表达乳腺癌的临床研究 癌 因此，这项建议的最终目的是扩大和 确定E1 A基因对人乳腺癌的抗癌活性 通过将其与化疗剂或p53基因组合来治疗癌症，以及 阐明其细胞毒性机制。 拟议的实验旨在 将基础研究成果转化为临床应用 治疗剂。 他们希望这种新颖的方法能够应用于 E1 A基因治疗的II期研究，提高疗效， 血液和骨髓剂量强化化疗的远期疗效 移植与E1 A基因治疗的联合应用。

DESCRIPTION (Applicant's Description): Career Goal: The applicant's career goal is to become an established physician-scientist at an academic institution in a field of therapy that relates to the use of molecular biology techniques in medical oncology. He especially hopes that he can be involved in translational breast cancer research related to dose-intensive chemotherapy with blood and marrow transplantation support. He firmly believes that understanding the molecular mechanisms of breast cancer will result in improved long-term, disease-free survival rate among patients with advanced breast cancer. To achieve this goal, he has enrolled in a Ph.D. program at The University of Texas Graduate School of Biomedical Sciences under the supervision of Mien Chie Hung, Ph.D. and is providing patient care as a staff member in the Department of Blood and Marrow Transplantation at The University of Texas M. D. Anderson Cancer Center. Proposal: Breast cancer is one of the most common causes of cancer mortality for women in the United States. The major cause of treatment failure in patients with breast cancer after dose-intensive chemotherapy still remains disease relapse, presumably due to the chemoresistance of residual breast cancer cells. Overexpression of the HER-2/neu oncogene occurs in 30% of breast cancers and has been associated with poor prognosis. This may be due to the fact that HER-2/neu induces resistance to chemotherapeutic agents. The adenovirus type 5 E1A gene product is known to repress HER-2/neu expression at a transcription level. The sponsor's laboratory has previously shown that HER-2/neu expression can be repressed in HER-2/neu overexpressing breast cancer cell lines using adenoviral vector or cationic liposome as a delivery system for the E1A gene. Recently, it has been reported that E1A s u ppresses tumorigenicity by a variety of mechanisms in addition to transcriptional repression of HER-2/neu. The applicants are currently conducting a phase I clinical trial of E1A gene therapy for patients with HER-2/neu-overexpressing breast cancer. Therefore, the ultimate goal of this proposal is to expand and establish the anti-oncogenic activity of the E1A gene against human breast cancer by combining it with chemotherapeutic agents or the p53 gene, and to elucidate their cytotoxic mechanism. The proposed experiments are aimed at translating the findings from basic research into clinically useful therapeutic agents. They hope that this novel approach will be applied to the phase II study of E1A gene therapy and improve the efficacy and the long-term outcome of dose-intensive chemotherapy with blood and marrow transplantation in breast cancer by combining them with E1A gene therapy.