Lymphatic Radiobiology

淋巴放射生物学

基本信息

批准号：
8326221
负责人：
TIMOTHY P PADERA
金额：
$ 23.75万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-12 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8326221
关键词：
Address Adenovirus Vector Adenoviruses Advocate Affect Aftercare Animal Model Animals Apoptotic Area Award Axilla Axillary Lymph Node Dissection Biochemistry Biological Assay Blood Caliber Cancer Patient Cell Death Cell Proliferation Cell division Cells Cessation of life Commit Complement Complication Data Dermal Development Dose Ear Endothelial Cells Engineering Equipment Exposure to Failure Fibroblast Growth Factor 2 Future General Hospitals Goals Growth Growth Factor Growth Factor Receptors Human Image Imaging technology Immunohistochemistry In Vitro Incidence Incubated Infection Ionizing radiation K-Series Research Career Programs Kinetics Laboratories Lead Light Lymphangiogenesis Lymphangiography Lymphatic Lymphatic Endothelial Cells Lymphatic vessel Lymphedema Malignant Neoplasms Measures Mediating Mentors Mentorship Methods Mitosis Mitotic Molecular Molecular Biology Molecular Target Monitor Mus Nature Necrosis Neuropilin-1 Neuropilin-2 Operative Surgical Procedures Pain Pathway interactions Patients Phase Pre-Clinical Model Prevention Prior Therapy Proliferating Radiation Radiation Tolerance Radiation induced damage Radiation therapy Radiation-Sensitizing Agents Radiobiology Relative (related person)Research Research Personnel Research Training Risk Seeds Signal Pathway Signal Transduction Signaling Molecule Staining method Stains Swelling Techniques Testing Therapeutic Tissues Training United States Vascular Endothelial Cell Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor C Vascular Endothelial Growth Factor Receptor-1 Vascular Endothelial Growth Factor Receptor-2 Vascular Endothelial Growth Factor Receptor-3 Venous Woman Work cancer cell career design experience fibroblast growth factor receptor 3 genetic manipulation in vitro Model in vivo inhibitor/antagonist intravital microscopy irradiation knowledge base lymph flow malignant breast neoplasm novel prevent radiation effect repaired research study response senescence skills small hairpin RNA success time use tool treatment planning

项目摘要

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.

乳腺癌患者进行手术的腋窝辐射通常会导致淋巴水肿，这几乎影响美国有40万名妇女。淋巴水肿是毁容的，疼痛的，并且形成了感染的Nidus。作为目前的治疗几乎没有减轻许多患者，开发预防和预防方法至关重要逆转淋巴水肿的形成。淋巴管生长因子的使用来刺激淋巴生长并且已经提倡反向淋巴水肿。但是，在癌症患者中，这种策略可能有助于癌细胞进一步扩散。为了避免这种并发症，我们专注于预防淋巴水肿独立奖。虽然提供了许多组织的放射敏感性的信息，但辐射对淋巴的影响船只在很大程度上没有报道。在此提案中，我们将研究淋巴的放射敏性内皮细胞及其对辐射的细胞和分子反应。然后，我们将改变淋巴内皮细胞放射敏感性通过暴露于生长因子或生长因子的遗传操纵信号。我们将通过测量正常和增殖的放射敏感性来补充这些研究体内淋巴管。最后，我们将防止通过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引起的损伤的策略，以防止淋巴水肿患者。我将在E.L.中完成此werl。 Iviassachusetts综合医院的Steele Laboratories 拟议的实验所需的优义动物智能和内加成像设备。我的导师，博士。 Brian Seed和Kathryn Held将继续与我合作，致力于发展我的职业生涯，并将帮助我过渡到成功的独立学术研究员。