Lymphatic Radiobiology

淋巴放射生物学

• 批准号: 7686725
• 负责人: TIMOTHY P PADERA
• 金额: $ 14.26万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-12 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7686725
• 关键词: Address; Adenovirus Vector; Adenoviruses; Advocate; Affect; Aftercare; Animal Model; Apoptotic; Area; Arts; Award; Axilla; Axillary Lymph Node Dissection; Biochemistry; Biological Assay; Biology; Bite; Blood; Caliber; Cancer Patient; Cell Death; Cell division; Cells; Cessation of life; Commit; Complement; Complication; Data; Dermal; Development; Dose; Ear; Endothelial Cells; Engineering; Exposure to; Faculty; Failure; Fibroblast Growth Factor 2; Funding Opportunities; Future; General Hospitals; Goals; Growth; Growth Factor; Growth Factor Receptors; Human; Imaging technology; Immunohistochemistry; In Vitro; Incidence; Incubated; Infection; Institutes; Ionizing radiation; K-Series Research Career Programs; Kinetics; Knowledge; Laboratories; Lead; Leg; Light; Lymphangiogenesis; Lymphangiography; Lymphatic; Lymphatic Endothelial Cells; Lymphatic vessel; Lymphedema; Malignant Neoplasms; Massachusetts; Measures; Mediating; Mentors; Mentorship; Methods; Mitosis; Mitotic; Molecular; Molecular Biology; Molecular Target; Monitor; Mus; Nature; Necrosis; Neoplasm Metastasis; Neuropilin-1; Neuropilin-2; Operative Surgical Procedures; Pain; Pathway interactions; Patients; Phase; Positioning Attribute; Pre-Clinical Model; Prevention; Prior Therapy; Proliferating; Radiation; Radiation Tolerance; Radiation induced damage; Radiation therapy; Radiation-Sensitizing Agents; Radiobiology; Relative (related person); Research; Research Activity; Research Personnel; Research Training; Resources; Risk; Secure; Seeds; Signal Pathway; Signal Transduction; Signaling Molecule; Staining method; Stains; Swelling; Techniques; Technology; Testing; Therapeutic; Tissues; Training; United States; Universities; 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; medical schools; novel; prevent; programs; radiation effect; repaired; research study; response; senescence; skills; small hairpin RNA; success; time use; tool; treatment planning

DESCRIPTION (provided by applicant): 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 moecular response to radiation (Aim 1, Mentored Phase). We will then alter lymphatic endothelial cell radiosensitivity through exposure to growth factors or genetic manipulation of growth factor signaling (Aim 2, Independent Phase). We will complement these studies by measuring the radiosensitivity of normal and proliferating lymphatic vessels in vivo (Aim 3, Independent Phase). Finally, we will prevent radiation induced damage of lymphangiogenic vessels by administering inhibitors of lymphatic growth factor receptors (Aim 3, Independent Phase). 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 the Mentored Phase at Massachusetts General Hospital under the guidance of Dr. Brian Seed (Mentor) and Dr. Kathy Held (Co-mentor). I will use this Mentored Phase to strengthen my knowledge of molecular biology and biochemistry, and radiobiology, the respective expertises of my mentors. During this period I will have the resources of the E.L. Steele Laboratory and those of my mentors available, as well as many educational and training opportunities at Harvard University, Harvard Medical School and Massachusetts Institute of Technology. My mentors are committed to the development of my career and will help my transition into a successful independent academic researcher. I will secure an independent faculty position for the Independent Period of this Award. I will also vigorously pursue other funding opportunities to support additional research activities in lymphatic biology and cancer metastasis during this period. By the end of the term of this Award, I intend to have established a strong independent research program. Relevance: Nearly 400,000 breast cancer patients in the United States develop lymphedema after axillary radiation. Lymphedema treatments are generally designed to control swelling and minimize the pain associated with lymphedema, but these treatments are only marginally effective. Understanding the response of lymphatic vessels to radiation will help design strategies to prevent lymphedema formation in breast cancer patients.

描述（由申请人提供）：乳腺癌患者腋窝放射手术常导致淋巴水肿，在美国影响近40万妇女。淋巴水肿会造成毁容、疼痛并形成感染病灶。由于目前的治疗方法对许多患者几乎没有缓解作用，因此开发预防和逆转淋巴水肿形成的方法至关重要。提倡使用淋巴管生成生长因子来刺激淋巴生长和逆转淋巴水肿。然而，在癌症患者中，这种策略可能会促进癌细胞的进一步扩散。为了避免这种并发症，我们将重点放在淋巴水肿的预防上。