Clinicopathology of IGF2 loss of imprinting in colon neoplasia

结肠肿瘤中 IGF2 印记缺失的临床病理学

• 批准号: 7197075
• 负责人: MARCIA Roxana CRUZ-CORREA
• 金额: $ 15.82万
• 依托单位: UNIVERSITY OF PUERTO RICO MED SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-02 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7197075
• 关键词: Apoptosis; Award; Biological Markers; Blood Vessels; Cancer Patient; Cell Proliferation; Characteristics; Clinic; Clinical; Clinical Research; Clinical Trials; Colon; Colonic Neoplasms; Colorectal; Colorectal Cancer; Colorectal Neoplasms; Commit; Comprehensive Cancer Center; Development; Diffuse; Doctor' s Degree; Drug or chemical Tissue Distribution; Environmental Exposure; Epigenetic Process; Esophagus; Fellowship; Florida; Gastroenterology; Genomic Imprinting; Genus Cola; Goals; IGF2 gene; Individual; Inherited; Insulin-Like Growth Factor II; Investigation; Laboratories; Laboratory Personnel; Malignant Neoplasms; Medical Surveillance; Medicine; Mentors; Molecular; Mucous Membrane; Outcome; Patients; Peptides; Peripheral Blood Lymphocyte; Phenotype; Postoperative Period; Predisposition; Prevention; Public Health Schools; Puerto Rico; Rate; Rectal Cancer; Recurrence; Research Institute; Research Personnel; Resources; Risk; Risk Factors; Role; S-Phase Fraction; Screening procedure; Serum; Small Intestines; Somatomedins; Stomach; Stratification; Syndrome; System; Testing; Time; Tissues; Universities; Visit; Work; angiogenesis; cancer recurrence; carcinogenesis; career; case control; density; design; gastrointestinal; imprint; indexing; oncology; peripheral blood; professor; programs; skills; tumor

DESCRIPTION (provided by applicant): Dr. Cruz-Correa is currently an Associate Professor of Medicine at the University of Puerto Rico Comprehensive Cancer Center (UPRCCC) and visiting Assistant Professor of Medicine at Johns Hopkins University (JHU). She completed a gastroenterology fellowship at JHU and finished a doctorate degree in Clinical Investigation at the Johns Hopkins Bloomberg School of Public Health, while completing her current K07 NCI Mentored Award. Her immediate career goals are to transition into an independent investigator having the financial and time resources to complete her current hypothesis in a timely fashion. Her long-term objectives are to become a leader in the field of gastrointestinal oncology with emphasis in epigenetics, clinical outcomes and prevention. Specifically, Dr. Cruz-Correa envisions a translational gastrointestinal research institute integrated by: (1) a basic laboratory unit, and (2) a clinical research unit, working together evaluating multiple hypotheses to sequentially elucidate mechanisms of gastrointestinal carcinogenesis. The UPRCCC is fully committed to the development of Dr. Cruz-Correa's career, and will provide all the needed personnel, laboratory, clinical resources as well as the protected time required for successful completion of this investigation. This award will enable her to continue to develop the necessary skills for a successful independent career in clinical research with the support of her current mentors and co-investigators, Dr. Francis Giardiello, Dr. Andrew Feinberg (Johns Hopkins University), Dr. Steven Wexner (Cleveland Clinic Florida), and Dr. Reynold Lopez (UPRCCC). This project will test the hypothesis that abnormal imprinting of the IGF2 gene is a biomarker for colorectal cancer (CRC) predisposition, with a diffuse tissue distribution, which exerts its increased risk via the IGF axis, resulting in specific pathological and molecular characteristics and a unique CRC phenotype. Loss of imprinting (LOI) of IGF2 is an independent risk factor for CRC, but the underlying carcinogenic mechanisms remain unclear. LOI of IGF2 is present in the peripheral blood lymphocytes (PBL) of patients with CRC and is not associated with common environmental exposures. This investigation will determine the clinicopathological impact of LOI of IGF2 and delineate the underlying molecular mechanisms of the IGF2 system in CRC patients using a feasible cross-sectional and matched case-control design. Specifically, it will evaluate the association of LOI of IGF2 with the IGF2 peptide, proliferation index, apoptosis index and micro-vascular density in CRC patients. It will also examine the association between LOI and rectal cancer recurrence. LOI of IGF2 has potential as a new biomarker for colorectal cancer predisposition, and may change our current risk-stratification, screening, and surveillance colorectal cancer paradigms.

描述（由申请人提供）：Cruz-Correa博士目前是波多黎各大学综合癌症中心（UPRCCC）的医学副教授和约翰霍普金斯大学（JHU）的医学客座助理教授。她在JHU完成了胃肠病学奖学金，并在约翰霍普金斯彭博公共卫生学院完成了临床研究博士学位，同时完成了她目前的K 07 NCI指导奖。她近期的职业目标是成为一名独立的调查员，拥有足够的财力和时间来及时完成她目前的假设。她的长期目标是成为胃肠道肿瘤学领域的领导者，重点是表观遗传学，临床结果和预防。具体来说，Cruz-Correa博士设想建立一个转化型胃肠道研究所，由（1）一个基础实验室单位和（2）一个临床研究单位组成，共同评估多个假设，依次阐明胃肠道致癌机制。UPRCCC完全致力于Cruz-Correa博士的职业发展，并将提供成功完成本研究所需的所有必要人员、实验室、临床资源以及受保护的时间。该奖项将使她能够继续发展必要的技能，在她目前的导师和合作研究者，弗朗西斯Giardiello博士，安德鲁·范伯格博士（约翰霍普金斯大学），史蒂芬·韦克斯纳博士（克利夫兰诊所佛罗里达）和Dr. Alfred洛佩斯博士（UPRCCC）的支持下，在临床研究中取得成功的独立职业生涯。 该项目将测试IGF 2基因的异常印迹是结直肠癌（CRC）易感性的生物标志物的假设，具有弥漫性组织分布，通过IGF轴发挥其增加的风险，导致特定的病理和分子特征以及独特的CRC表型。IGF 2印迹缺失（LOI）是CRC的独立危险因素，但潜在的致癌机制仍不清楚。IGF 2的LOI存在于CRC患者的外周血淋巴细胞（PBL）中，并且与常见的环境暴露无关。这项研究将确定IGF 2 LOI的临床病理学影响，并使用可行的横断面和匹配的病例对照设计描述CRC患者IGF 2系统的潜在分子机制。具体而言，它将评估CRC患者中IGF 2的LOI与IGF 2肽、增殖指数、凋亡指数和微血管密度的相关性。它还将检查LOI和直肠癌复发之间的关联。IGF 2的LOI有可能作为结直肠癌易感性的新生物标志物，并可能改变我们目前的风险分层，筛查和监测结直肠癌的模式。