Lymphatic Radiobiology

乳腺癌患者手术后的腋窝放射治疗通常会导致水肿， 在美国有40万女性。淋巴水肿是毁容，疼痛，并形成一个病灶的感染。作为 目前的治疗方法对许多患者几乎没有缓解作用，因此开发预防和治疗方法至关重要， 逆转水肿的形成。使用淋巴管生成因子刺激淋巴管生长 并主张逆转水肿。然而，在癌症患者中，这种策略可能有助于 癌细胞的进一步扩散。为了避免这种并发症，我们在本研究中重点关注水肿预防。 通往独立奖之路 虽然许多组织的辐射敏感性的信息是可用的，辐射对淋巴细胞的影响， 船只基本上没有报告。在这个建议中，我们将研究淋巴细胞的放射敏感性， 内皮细胞及其对辐射的细胞和分子反应。然后我们将改变淋巴 通过暴露于生长因子或生长因子的遗传操作的内皮细胞放射敏感性 发信号。我们将通过测量正常和增殖细胞的放射敏感性来补充这些研究。 体内淋巴管。最后，我们将通过以下措施预防辐射引起的淋巴管生成血管损伤： 施用淋巴生长因子受体的抑制剂。该项目的最终目标是确定 保护淋巴管免受辐射诱导的损伤，以预防 患者 我将在地球上完成这个世界。斯蒂尔实验室在IVIAssassy总医院，其中有 批准拟议实验所需的动物设施和活体成像设备。我 Brian Seed博士和Kathryn Held博士将继续与我在这个项目上合作， 致力于我的职业发展，并将帮助我过渡到一个成功的独立 学术研究者

Axillary radiation with surgery in breast cancer patients often leads to lymphedema, which affects nearly 400,000 women in the United States. Lymphedema is disfiguring, painful and forms a nidus for infection. As current treatments provide little relief for many patients, it is critical to develop methods to prevent and reverse the formation of lymphedema. The use of lymphangiogenic growth factors to spur lymphatic growth and reverse lymphedema has been advocated. However, in cancer patients this strategy may facilitate the further spread of cancer cells. To avoid this complication, we focus on lymphedema prevention in this Pathway to Independence Award. While information on the radiosensitivity of many tissues Is available, the effects of radiation on lymphatic vessels have been largely unreported. In this proposal we will study the radiosensitivity of lymphatic endothelial cells and their cellular and molecular response to radiation. We will then alter lymphatic endothelial cell radiosensitivity through exposure to growth factors or genetic manipulation of growth factor signaling. We will complement these studies by measuring the radiosensitivity of normal and proliferating lymphatic vessels In vivo. Finally, we will prevent radiation-induced damage of lymphangiogenic vessels by administering inhibitors of lymphatic growth factor receptors. The ultimate goal of this project is to identify strategies to protect lymphatic vessels from radiation-induced damage in order to prevent lymphedema in patients. I will complete this worl< in the E.L. Steele Laboratories at IVIassachusetts General Hospital, which has the approriate animal faciiities and intravital Imaging equipment necessary for the proposed experlmeints. My mentors, Drs. Brian Seed and Kathryn Held, will continue to collaborate with me on this project and are committed to the development of my career and will help my transition into a successful independent academic researcher.