FATTY ACIDS AND PPARS IN BREAST CANCER PREVENTION

乳腺癌仍然是美国女性癌症死亡的第二大原因。需要采取副作用最小的预防措施，以减少乳腺癌的发病率和进展。首席研究员易博士的长期研究目标是研究乳腺癌进展的分子机制，并最终开发预防和根除乳腺癌的新干预措施。易博士正在申请资金，以发展她在乳腺癌预防和控制方面的技能，这一努力将补充她作为乳腺癌专业外科医生的培训，并使她能够在未来开展对降低乳腺癌风险至关重要的转化性研究。她在预防肿瘤学方面的培训将包括俄亥俄州立大学、综合癌症中心和詹姆斯癌症医院和索洛夫研究所的精选教师的指导，结合教学课程工作和癌症预防研究项目。该计划整合了分子遗传学、营养科学和乳腺癌临床研究。过氧化物酶体增殖物激活受体(PPAR)是一种核受体，能刺激脂肪酸和前列腺素等配体的转录活性。PPARGamma亚型调节正常和恶性组织中的细胞分化和增殖。细胞培养和动物模型将被用来评估脂肪酸对乳腺癌PPAR伽马激活的影响。人类乳腺肿瘤和周围的脂肪和上皮组织也将被评估PPAR的表达模式和其他影响PPAR激活的因素。这项工作将有助于产生数据，以支持关于饮食脂肪和PPAR伽马对乳腺癌进展的影响的前瞻性临床研究。结合在刺激的科学和临床环境中的教学课程，该项目将为易博士提供所需的培训，使其成为预防肿瘤学领域的独立临床科学家。

Breast cancer remains the second leading cause of cancer death of women in the United States. Preventive measures with minimal adverse effects are needed to reduce the incidence and progression of breast cancer. The long-term research goal of the principal investigator, Dr. Yee, is to investigate the molecular mechanisms of breast cancer progression and ultimately develop new interventions for breast cancer prevention and eradication. Dr. Yee is requesting funds to develop her skills in breast cancer prevention and control, an effort that will complement her training as a surgeon specializing in breast cancer and allow her to conduct the future translational research vital to reducing breast cancer risk. Her training in preventive oncology will encompass mentorship by select faculty of The Ohio State University, Comprehensive Cancer Center and James Cancer Hospital and Solove Research Institute, combining didactic course work and a cancer prevention research project. The plan integrates molecular genetics, nutritional sciences, and clinical breast cancer research. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that stimulate transcriptional activity in response to ligands such as fatty acids and prostaglandins. The PPARgamma subtype regulates cell differentiation and proliferation in normal and malignant tissues. Cell culture and animal models will be used to evaluate fatty acid effects on PPARgamma activation in breast cancer. Human breast tumors and surrounding fat and epithelial tissue will also be assessed for patterns of expression of PPARs and other factors affecting PPAR activation. This work will serve to generate data to support a prospective clinical study of the effects of dietary fat and PPARgamma on breast cancer progression. Combined with a didactic course of study in a stimulating scientific and clinical environment, this project will give Dr. Yee the training required to become an independent clinician scientist in the field of preventive oncology.