BREAST CANCER LYMPHEDEMA: ROLE OF INSULIN RESISTANCE/FOXC2

乳腺癌淋巴水肿：胰岛素抵抗/FOXC2 的作用

基本信息

批准号：
7717890
负责人：
Stanley G Rockson
金额：
$ 0.09万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-12-01 至 2008-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7717890
关键词：
5&apos Untranslated Regions Blood Blood specimen Cancer Survivor Clinical Clinical assessments Collection Computer Retrieval of Information on Scientific Projects Database Edema Evaluation Experimental Designs Funding Future Genes Genetic Polymorphism Glucose Grant Health Hour Human Infusion Pumps Institution Insulin Insulin Resistance Ipsilateral Lead Limb structure Lymphedema Measurement Modification OGTT Octreotide Oral Patients Physical Examination Rate Relative (related person)Research Research Personnel Resources Risk Role Sampling Serum Albumin Solutions Source Standards of Weights and Measures Stratification Study Subject Testing Therapeutic Intervention Time United States National Institutes of Health Upper Extremity Upper arm Venous Visit glucose uptake insulin secretion insulin sensitivity malignant breast neoplasm peripheral blood

项目摘要

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.

该子项目是利用该技术的众多研究子项目之一资源由 NIH/NCRR 资助的中心拨款提供。研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金，因此可以出现在其他 CRISP 条目中列出的机构是。对于中心来说，它不一定是研究者的机构。假设：我们的目标是：1）对晚期乳腺癌幸存者的胰岛素敏感性进行定量评估，在有同侧手臂水肿临床证据的受试者和没有同侧手臂水肿临床证据的受试者之间平均分配，2）相对胰岛素抵抗（IR）存在的相关性）对乳腺癌相关淋巴水肿的表达，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，我们将对每位患者的 FOXC2 基因（包括非翻译 5' 区域）进行测序，以确定可能与 IR 和淋巴水肿风险的存在相关的潜在多态性。实验设计：在初次访视中，每个研究对象将接受一般健康状况的临床评估，包括体检和根据肢体周长的卷尺测量估算上肢体积的评估，并将获取外周血样本用于 FOXC2 基因分析。在第二次访视中，将通过对最初描述的胰岛素抑制试验（IST）进行修改来评估胰岛素敏感性，在禁食过夜后，将奥曲肽溶解在含有 2.5 的溶液中。 % (w/v) 人血清白蛋白将以 25 ¿ g/hr，通过哈佛输液泵抑制内源性胰岛素分泌，同时分别以 25 mU/m2/min 和 240 mg/m2/min 的速度输注血液，直至 150 分钟。进入测试，然后在测试的最后 30 分钟内每十分钟一次。在第三次（最后一次）访视中，每位受试者将接受标准口服葡萄糖耐量测试。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 120 时间采集静脉血。 180 分钟