Robert Bast, Jr.
教授
The University of Texas MD Anderson Cancer Center
实验治疗系
Our laboratory is addressing three of the critical problems in the management of ovarian cancer, including late detection, drug resistance and tumor dormancy, while attempting to understand the heterogeneity of ovarian cancers at a cellular and molecular level.
欢迎受训者的项目包括：
1。Function of imprinted tumor suppressor genes that are downregulated in ovarian cancer。在过去的十年里,我们已经确定了几个imprinted tumor suppressor genes whose expression is decreased or lost in ovarian cancer. Among these, we have best characterized ARHI (DIRAS3) which encodes a 26kD GTPase with 50% homology to Ras, but with an opposite function that can be attributed to a 34 amino acid N terminal extension. ARHI is downregulated in 60% of ovarian cancers associated with decreased disease free survival. Expression from the single functioning allele can be inhibited by LOH, hypermethylation or transcriptional regulation by E2F1 or E2F4 in different cancers. Re-expression of ARHI inhibits proliferation and motility while inducing autophagy and tumor dormancy. Current studies, funded by an R01, concern mechanisms underlying ARHI-induced autophagy and requirements for survival of dormant ovarian cancer cells. For these studies, we have developed the first inducible model for tumor dormancy in ovarian cancer.
2。不同卵巢癌中对紫杉醇的主要敏感性的个性化增强。Through a high throughput kinome siRNA screen, my laboratory has identified more than 30 kinases that regulate paclitaxel sensitivity in ovarian cancer cell lines by modulating centrosome function (SIK2), paclitaxel retention (CDK5) or microtubule stability (ILK, FER). Both fundamental studies of mechanism and translational studies of siRNA therapy in combination with paclitaxel are being pursued.
3。鉴定生物标志物和早期发现卵巢癌的策略。在开发了用于监测卵巢癌的CA125血清测定方面，我们已经测试了大约115个潜在的生物标志物，以鉴定四个生物标志物板用于早期疾病。目前，我们正在测试几个这样的小组，以了解其能够区分临床前和早期疾病与健康女性的女性。在卵巢孢子的支持下，在3000名看似健康的绝经后妇女中正在进行一项多年筛查试验，以评估一小部分生物标志物水平上升的妇女的超声的特异性和积极预测价值。迄今为止，该试验已促使8例操作发现5例卵巢癌病例，均在早期，与37％的正预测值相一致，即每例卵巢癌只有3例手术。为了促进这些研究，我们正在与赖斯的研究人员合作，将测定在纳米比奥芯片上进行测试。蛋白质表达阵列的最新研究已经确定了一组115种自动抗体，该抗体有望在较大的女性中检测到临床前疾病。
我们实验室中的一个教程将提供有关ARHI诱导的自噬和对休眠卵巢癌细胞生存的要求的经验，对卵巢癌和紫杉醇结合的siRNA治疗的基础研究以及siRNA治疗的转化研究。此外，学生将能够学习鉴定卵巢癌的生物标志物。通过我们的每周实验室研讨会，学生还将获得准备和介绍科学演讲的经验。
教育与培训
医学博士 - 哈佛医学院 - 1971年