Hepatic steatosis promotes liver metastasis

肝脂肪变性促进肝转移

• 批准号: 10365691
• 负责人: Steven L Teitelbaum
• 金额: $ 45.72万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10365691
• 关键词: Address; Adipose tissue; Affect; American; Breast Cancer Patient; Breast Cancer Risk Factor; Breast Cancer Treatment; Breast cancer metastasis; Calories; Cancer Prognosis; Data; Diagnosis; Disseminated Malignant Neoplasm; Early treatment; Energy-Generating Resources; Environment; Enzymes; Event; Exhibits; Fatty Acids; Fatty Liver; Goals; Grant; Growth; Health; Hepatic; Hepatocyte; High Fat Diet; Histology; Human; Immune; Institutes; Intake; Lipids; Lipolysis; Liver; Magnetic Resonance Imaging; Malignant Neoplasms; Metabolic; Metabolic syndrome; Metastatic Neoplasm to the Liver; Metastatic breast cancer; Mitochondria; Modeling; Mus; Neoplasm Metastasis; Obesity; Patients; Phenotype; Predisposition; Prevention; Process; Prognosis; Property; Resistance; Role; Site; Societies; Therapeutic; Tissue Transplantation; Triglycerides; Tumor Burden; Tumor-associated macrophages; Weight; Woman; breast cancer survival; cancer cell; chemotherapy; fatty liver disease; glucose metabolism; improved; liver biopsy; macrophage; malignant breast neoplasm; neoplastic cell; non-alcoholic fatty liver disease; oxidation; prevent; response; targeted treatment; tumor; tumor growth; tumor microenvironment

Project Summary/Abstract Treatment of early stage breast cancer has substantially improved but preventing metastasis remains a more elusive target. Obesity, which is endemic in our society, is associated with an increased risk of breast cancer and accelerated metastasis. The means by which obesity compromises survival of breast cancer patients is, however, poorly understood. Liver is among the most common sites of breast cancer metastasis and its occurrence is generally associated with poor prognosis. Liver health is closely related to weight as obesity is the major cause of fatty liver disease, estimated to be present in 1/4 to 1/3 of Americans. We discovered that fatty liver disease markedly increases liver metastasis, in mice, by providing fuel to tumor cells thereby accelerating their growth. Examination of human liver biopsies and MRI analysis suggests the same is true in women with metastatic breast cancer. Thus, our first goal is to determine if treating fatty liver disease reduces breast cancer liver metastasis and improves its response to chemotherapy. To identify potential new treatments for liver metastasis we will explore the mechanisms by which fatty liver disease stimulates tumor growth. Finally, we will ask if human breast cancers exhibit the same liver metastatic properties as those arising in mice. If our conclusion proves true, treatment of breast cancer will universally require prevention and treatment of fatty liver disease and therefore impact all affected women. Prevention and treatment of fatty liver disease in breast cancer patients, however, may likely reduce liver metastasis and therefore prolong survival. Because fatty liver disease is most often the product of obesity, educating patients about calorie intake, which can be instituted immediately, may have significant effects on breast cancer prognosis.

项目概要/摘要 早期乳腺癌的治疗已显着改善，但预防转移仍然是一个更重要的问题 难以捉摸的目标。肥胖在我们的社会中很普遍，与乳腺癌风险增加有关 并加速转移。肥胖影响乳腺癌患者生存的方式是， 然而，了解甚少。肝脏是乳腺癌最常见的转移部位之一，其 发生通常与不良预后相关。肝脏健康与体重密切相关，因为肥胖是 脂肪肝的主要原因，估计有 1/4 至 1/3 的美国人患有脂肪肝。 我们发现，脂肪肝疾病通过为肿瘤提供燃料，显着增加小鼠的肝转移 从而加速细胞的生长。人类肝脏活组织检查和 MRI 分析表明同样的情况 对于患有转移性乳腺癌的女性来说也是如此。因此，我们的首要目标是确定是否可以治疗脂肪肝 减少乳腺癌肝转移并改善其对化疗的反应。识别潜在的新 肝转移治疗我们将探讨脂肪肝刺激肿瘤的机制 生长。最后，我们要问人类乳腺癌是否表现出与乳腺癌相同的肝转移特性。 在小鼠中。如果我们的结论成立，乳腺癌的治疗将普遍需要预防和治疗 脂肪肝疾病，因此影响所有受影响的女性。脂肪肝的预防和治疗 然而，乳腺癌患者可能会减少肝转移，从而延长生存期。因为胖 肝脏疾病通常是肥胖的产物，可以对患者进行有关卡路里摄入量的教育 立即，可能对乳腺癌预后产生显着影响。