Folate Targeted Delivery of a CDKI

描述（由申请人提供）：卵巢癌是第二大最常见的妇科恶性肿瘤，是女性癌症死亡的第四大原因。卵巢癌是第二大最常见的妇科恶性肿瘤，也是导致妇女癌症死亡的第四大原因。2002年，全国将新增2.34万例卵巢癌病例，1.39万名妇女将死于卵巢癌。只有25%的病例在早期被发现（美国癌症协会，2002年）。75%的卵巢癌患者出现晚期疾病，不到40%的患者能存活5年。这些结果在过去四十年中仅略有改善，需要新的治疗方式来影响这种疾病。我们的长期目标是提高卵巢癌患者的生存率。我们的目的是在卵巢癌模型系统中使用叶酸靶向细胞生长抑制剂来抑制肿瘤细胞。我们的假设是，叶酸靶向脂质体含有稳定版本的周期蛋白依赖性激酶抑制剂p27Kip1，将阻止肿瘤细胞在体内的生长。提出这项研究的基本原理是，在晚期卵巢癌妇女的腹膜腔中发现一种有效的治疗卵巢癌的方法，将增加卵巢癌妇女的生存率。我们的研究团队非常适合承担这项任务。这家名为Endocyte的小公司是叶酸靶向脂质体基因递送领域的领导者。学术研究人员带来了p27Kip1控制肿瘤细胞生长的机制基础方面的知识和经验，并获得了监测体内肿瘤细胞生长的成像设备核心。为了验证我们的假设，提出了以下具体目标：目标1：分析叶酸靶向脂质体将p27Kip1递送到培养的致瘤细胞系中。目的2：在卵巢癌模型系统和目的3中评估叶酸/脂质体/p27Kip1治疗后的肿瘤进展。利用体内成像技术分析叶酸/脂质体p27kip1治疗后的肿瘤生长情况。

DESCRIPTION (provided by applicant): Ovarian cancer is the second most common gynecological malignancy and is the fourth leading cause of cancer mortality in women. Ovarian cancer is the second most common gynecological malignancy and is the fourth leading cause of cancer mortality in women. Nationwide 23,400 new cases will be diagnosed in 2002 and 13,900 women will die of ovarian cancer. Only 25% of all cases are detected at an early stage (American Cancer Society, 2002). Seventy five percent of patients with ovarian cancer present with advanced disease and less than 40% survive 5 years. These results have improved only slightly over the last four decades and new treatment modalities are needed to impact this disease. Our long-term goal is to improve the survival rate of women who have ovarian cancer. Our objective in this application is to use folate to target a cell growth inhibitor to tumor cells in an ovarian cancer model system. Our hypothesis is that folate-targeted liposomes containing a stabilized version of the cyclin dependent kinase inhibitor, p27Kip1, will block tumor cell growth in vivo. The rationale for the proposed studies is that an effective therapy for the treatment of ovarian cancer found in the peritoneal cavity of women with advanced ovarian cancer will increase the survival rate of women with ovarian cancer. Our research team is uniquely suited to undertake this proposal. The small business, Endocyte, is a leader is the field of folate-targeted liposome gene delivery. The academic investigators bring knowledge and experience in the mechanistic basis of p27Kip1's control of tumor cell growth along with access to an imaging facility core for monitoring in vivo tumor cell growth. To test our hypothesis, the following specific aims are proposed: Aim 1: Analyze folate-targeted liposome delivery of p27Kip1 into cultured tumorigenic cell lines. Aim 2: Evaluate tumor progression after folate/liposome/p27Kip1 treatment in an ovarian cancer model system and Aim 3. Analyze tumor growth after folate/liposomelp27Kip1 treatment using in vivo imaging technology.