首页> 外文学位 >Metabolic Profiling of Urine, Fecal, and Serum Samples and Pancreatic Tumors and Evaluation of HMGA1 Expression Levels in Pancreatic Intraepithelial Neoplasia Cells in the Ptf1a-Cre; LSL-KrasG12D Transgenic Mouse Model of Pancreatic Cancer
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Metabolic Profiling of Urine, Fecal, and Serum Samples and Pancreatic Tumors and Evaluation of HMGA1 Expression Levels in Pancreatic Intraepithelial Neoplasia Cells in the Ptf1a-Cre; LSL-KrasG12D Transgenic Mouse Model of Pancreatic Cancer

机译:Ptf1a-Cre胰腺上皮内瘤变细胞中尿液,粪便和血清样品和胰腺肿瘤的代谢谱分析和HMGA1表达水平的评估; LSL-KrasG12D胰腺癌转基因小鼠模型

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摘要

Pancreatic cancer is the third leading cause of cancer related deaths. Individuals inflicted with this cancer are typically asymptomatic until advanced stages are reached. Surgical procedures provide the greatest chance of survival; nevertheless, pancreatic cancer is rarely detected in early stages where surgery would be effective. This is primarily due to the lack of dependable tests for early detection and diagnosis. Current diagnostic methods are extremely invasive or are deemed inadequate by general consensus, and population screening for pancreatic cancer with these methods is not feasible. Urine and fecal excrements have been shown to encompass potentially useful biomarkers in pancreatic cancer. I.;n this dissertation, potential early biomarkers in serum, urine, and blood were identified through the use of the mouse model Ptf1aCre; LSL-KrasG12D of pancreatic cancer and nuclear magnetic resonance spectroscopy (NMR). Additionally, a histology atlas of pancreatic tissue was produced to aid in the evaluation of the precancerous stages, referred to as pancreatic intraepithelial neoplasia (PanIN). Due to the existence of multiple classification systems being in use, discrepancies among the field exist. The generated atlas will promote discussion and clarification of the PanIN stages. In order to acquire images, removal of the pancreas had to be performed. Due to the lack of peer-reviewed and high quality videos and instructions available, a manuscript accompanied by a video were produced to show the proper procedures to successfully remove the pancreas by dissection from a mouse. Also, high-mobility growth A1 protein (HMGA1), that has been linked to tumor progression in many cancers, had not been examined with the Ptf1aCre; LSL-KrasG12D mouse model until now. Elevated levels of HMGA1 have been shown to be present in as young as 5-months in the PanIN mice and in as old as 15-months when compared to normal un-transitioned pancreatic tissue. This dissertation encompasses many tools, platforms, and analyses assisting in the progression of early diagnostic pancreatic cancer research.
机译:胰腺癌是癌症相关死亡的第三大主要原因。罹患这种癌症的个体通常无症状,直到达到晚期为止。外科手术提供最大的生存机会;但是,在手术有效的早期阶段,很少检测到胰腺癌。这主要是由于缺乏用于早期检测和诊断的可靠测试。当前的诊断方法具有极强的侵害性或被普遍共识认为不足,并且用这些方法进行胰腺癌的人群筛查是不可行的。已显示尿液和粪便排泄物包括胰腺癌中潜在有用的生物标志物。在本文中,通过使用小鼠模型Ptf1aCre鉴定了血清,尿液和血液中潜在的早期生物标记物。胰腺癌的LSL-KrasG12D和核磁共振波谱(NMR)。另外,产生了胰腺组织的组织学图谱,以帮助评估癌前期,称为胰腺上皮内瘤变(PanIN)。由于使用了多个分类系统,因此该字段之间存在差异。生成的地图集将促进PanIN阶段的讨论和澄清。为了获取图像,必须切除胰腺。由于缺乏经过同行评审的高质量视频和说明,制作了带有视频的手稿,以显示通过解剖从小鼠中成功切除胰腺的正确程序。此外,Ptf1aCre尚未检查与许多癌症的肿瘤进展相关的高迁移率生长A1蛋白(HMGA1);到现在为止,LSL-KrasG12D鼠标模型。与正常的未转化胰腺组织相比,在PanIN小鼠中,HMGA1的水平高低出现在5个月之内,而在15个月大时存在。本文涵盖了许多有助于早期诊断胰腺癌研究进展的工具,平台和分析。

著录项

  • 作者

    Schmahl, Michelle J.;

  • 作者单位

    Miami University.;

  • 授予单位 Miami University.;
  • 学科 Chemistry.;Biochemistry.
  • 学位 Ph.D.
  • 年度 2018
  • 页码 313 p.
  • 总页数 313
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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