BREAST CANCER LYMPHEDEMA: ROLE OF INSULIN RESISTANCE/FOXC2

乳腺癌淋巴水肿：胰岛素抵抗/FOXC2 的作用

• 批准号: 7375315
• 负责人: Stanley G Rockson
• 金额: $ 0.76万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7375315
• 关键词: BREAST; CANCER; LYMPHEDEMA; ROLE; INSULIN

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypothesis: It is hypothesized that: 1) a quantitative assessment of insulin sensitivity in late breast cancer survivors, equally divided among subjects who display clinical evidence of ipsilateral arm edema and those that do not, and 2) correlation of the presence of relative insulin resistance (IR) to the expression of breast cancer-associated lymphedema, will lead to future elaboration of appropriate risk stratification and targeted therapeutic interventions. Additionally, we will sequence the FOXC2 gene, including the untranslated 5' region, in each patient to identify potential polymorphisms that might correlate both to the presence of IR and lymphedema risk. Experimental Design: In the initial visit, each study subject will undergo clinical assessment of general health, including a physical examination, and evaluation of upper extremity volume, estimated from tape measurements of limb circumference. A peripheral blood sample will be obtained for analysis of the FOXC2 gene. In the second visit, assessment of insulin sensitivity will be performed. The ability of insulin to promote glucose uptake will be estimated by a modification of the insulin suppression test (IST) as originally described. After an overnight fast, octreotide in a solution containing 2.5% (w/v) human serum albumin will be administered at a rate of 25 ¿g/hr by a Harvard infusion pump, to suppress endogenous insulin secretion. Simultaneously, insulin and glucose will be infused at 25mU/m2/min and 240 mg/m2/min, respectively. Blood will be sampled every half hour until 150 min into the test, and then every ten min in the last 30 min of the test. In the third (last) visit, each subject will undergo a standard oral glucose tolerance test. After an overnight fast, a 75 g oral glucose load will be administered, with subsequent venous blood collection at times 0, 30, 60, 120, and 180 min.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一，该子项目和研究者 (PI) 可能已从其他 NIH 来源获得主要资助，因此可以在其他 CRISP 机构中得到体现。所列出的内容适用于该中心，该中心不一定是研究者所在的机构 假设：有人提出：1）对晚期乳腺癌幸存者的胰岛素敏感性进行定量评估，在显示同侧手臂水肿临床证据的受试者中平均分配。以及2）相对胰岛素抵抗（IR）的存在与乳腺癌相关淋巴水肿的表达之间的相关性，将导致未来制定适当的风险分层和有针对性的治疗干预措施。此外，我们将对这些进行排序。 FOXC2 基因，包括未翻译的 5' 区域，在每个患者中识别可能与 IR 和淋巴水肿风险的存在相关的潜在多态性。 实验设计：在初次就诊时，每个研究对象将接受一般临床评估。健康状况，包括身体检查和上肢体积评估，通过测量肢体周长来评估外周血样本，以进行 FOXC2 基因分析。胰岛素促进葡萄糖摄取的量将通过最初描述的胰岛素抑制试验（IST）的修改来估计。 禁食过夜后，将以一定的速率施用含有 2.5%（w/v）人血清白蛋白的溶液中的奥曲肽。的二十五g/hr，通过哈佛输液泵抑制内源性胰岛素分泌，同时分别以 25mU/m2/min 和 240 mg/m2/min 的速度输注血液，直至 150 分钟。测试，然后在测试的最后 30 分钟内每 10 分钟进行一次。 在第三次（最后一次）访视中，每个受试者将在禁食一夜后进行标准口服葡萄糖耐量测试。将给予g口服葡萄糖负荷，随后在0、30、60、120和180分钟时采集静脉血。