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Hepatic steatosis promotes liver metastasis

肝脂肪变性促进肝转移

基本信息

批准号：
10545090
负责人：
Steven L Teitelbaum
金额：
$ 47.08万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
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/10545090
关键词：
Acceleration 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 Intake Lipids Lipolysis Liver Macrophage Magnetic Resonance Imaging Malignant Neoplasms Metabolic Metabolic syndrome Metastasis Induction Metastatic Neoplasm to the Liver Metastatic breast cancer Mitochondria Modeling Mus Neoplasm Metastasis Obesity Patients Phenotype Predisposition Prevention Probability Process Prognosis Property Resistance Role Site Societies Therapeutic Tissue Transplantation Triglycerides Tumor Burden Tumor Promotion Tumor-associated macrophages Weight Woman breast cancer survival cancer cell chemotherapy fatty liver disease glucose metabolism improved liver biopsy malignant breast neoplasm neoplastic cell non-alcoholic fatty liver disease oxidation prevent response targeted treatment tumor tumor growth tumor microenvironment

项目摘要

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.

项目总结/文摘