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Targeted hyperthermia in combination with chimeric TRAIL and chemotherapeutic agent treatment for colorectal liver metastasis

靶向热疗联合嵌合TRAIL及化疗药物治疗结直肠肝转移

基本信息

批准号：
9360701
负责人：
YONG J LEE
金额：
$ 7.82万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9360701
关键词：
ABL1 gene Adjuvant Apoptosis Applications Grants BCL2 gene Biochemical Cancer Etiology Cause of Death Cessation of life Chimeric Proteins Colorectal Colorectal Cancer Combined Modality Therapy Diagnosis Disease Drug Kinetics Excision Fc Immunoglobulins Fc domain Goals Grant Half-Life Hepatotoxicity Hyperthermia Immunocompetent Induction of Apoptosis Injectable Intravenous Bolus Isolated Hepatic Perfusion Large Intestine Carcinoma Life Ligands MAPK8 gene Malignant Neoplasms Metastatic Neoplasm to the Liver Modeling Molecular Neoadjuvant Therapy Operative Surgical Procedures Outcome Pathway interactions Patients Plasma Rattus Regimen Research Project Grants Serum Signal Transduction Signal Transduction Pathway TNF gene TNF-related apoptosis-inducing ligand TNFSF10 gene TRAF2 gene Techniques Testing Therapeutic Tumor Volume United States Unresectable Woman base c-abl Proto-Oncogenes cancer cell chemotherapeutic agent chemotherapy colon cancer patients combinatorial efficacy study hyperthermia treatment in vitro activity in vivo insight men multimodality new therapeutic target novel novel strategies oxaliplatin preclinical efficacy preclinical study systemic toxicity tumor tumor growth

项目摘要

Abstract Colorectal cancer is one of the most common cancers in both men and women in the United States and accounts for approximately 140,000 new cases annually. Hepatic metastasis, the dominant feature of life- limiting disease, occurs in approximately 20–50% of patients with colorectal cancer. Although regional treatment options, including hyperthermic isolated hepatic perfusion (HIHP) and percutaneous IHP, offer the benefits of both aggressive local treatment and limited systemic toxicity, the management of unresectable colorectal liver metastases remains a major unsolved issue and more effective novel regimens are needed. During the grant period, we will develop a novel strategy for targeted HIHP therapy. We hypothesize that a combinatorial treatment of targeted hyperthermia, the biologic agent Fc-TRAIL (immunoglobulin Fc domain fused tumor necrosis factor-related apoptosis-inducing ligand), and the chemotherapeutic agent oxaliplatin will be effective in treating unresectable colorectal liver metastases. The specific aims of this project are to (1) elucidate the mechanism of synergistic anti-tumor efficacy caused by Fc-TRAIL-based targeted multimodal treatment, and (2) investigate the preclinical efficacy of this combinatorial treatment in an IHP rat model. The proposed studies for the first aim will employ biochemical and molecular techniques to investigate multimodal treatment. For the second aim, we will employ a syngeneic hepatic metastasis rat model of colorectal carcinoma to study the efficacy of the multimodal treatment. We believe that our proposed regimen will provide information on the potential therapeutic advantage of an Fc-TRAIL-based multimodal treatment on patients.

摘要