BREAST CANCER LYMPHEDEMA: ROLE OF INSULIN RESISTANCE/FOXC2

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 假设： 假设：1）对晚期乳腺癌幸存者的胰岛素敏感性进行定量评估，平均分为显示同侧手臂水肿临床证据的受试者和未显示同侧手臂水肿的受试者，以及2）相对胰岛素抵抗（IR）的存在与乳腺癌相关性水肿表达的相关性，将导致未来制定适当的风险分层和靶向治疗干预措施。 此外，我们将测序FOXC 2基因，包括非翻译的5'区，在每一个病人，以确定潜在的多态性，可能与IR和水肿风险的存在。 实验设计： 在初始访视中，每例研究受试者将接受一般健康状况的临床评估，包括体格检查和上肢体积评价（通过肢体周长的卷尺测量估计）。将采集外周血样本用于FOXC 2基因分析。 在第二次访视中，将进行胰岛素敏感性评估。胰岛素促进葡萄糖摄取的能力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，通过哈佛输注泵以25 μ g/hr的速率给予奥曲肽（溶于含2.5%（w/v）人血清白蛋白的溶液），以抑制内源性胰岛素分泌。同时，将分别以25 mU/m2/min和240 mg/m2/min输注胰岛素和葡萄糖。每半小时采集一次血样，直至试验开始后150分钟，然后在试验的最后30分钟内每10分钟采集一次血样。 在第三次（最后一次）访视中，每例受试者将接受标准口服葡萄糖耐量试验。禁食过夜后，将给予75 g口服葡萄糖负荷，随后在0、30、60、120和180 min时采集静脉血。

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 25 mU/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.