Liver metastasis is a common occurrence during the course of gastrointestinal disease. It has been found in 30-70% of patients who are dying of various malignancies including colorectal, breast, lung, and pancreas cancer. Surgery is a common therapy for liver metastasis;however, 5-year survival rates range from 25-40%, indicating the need to develop novel therapies. A part of developing novel therapies is the necessity to understand the development of liver metastasis. Kupffer cells (KC), the phagocytic cells of the liver, comprise approximately 10% of all hepatic cells. The role of KC in liver metastasis is not clearly understood;more specifically, it is not understood whether KC plays a defensive role against liver metastasis or enhances its angiogenesis. A better understanding of liver metastasis development and the role of KC is necessary to develop novel treatments for liver metastases. Another challenge in the treatment of cancers, including liver metastases, is the distribution of imaging and therapeutic agents to intended targets. Systemically administered drug molecules or contrast agents only reach their desired targets one part per 10,000-100,000. The overall goal of this project is to develop a broader understanding of physical barriers and biological factors involved in the progression of liver metastasis in orthotopic models of colorectal cancer and to design novel biocompatible delivery carriers able to overcome or take an advantage of these barriers with favorable pharmacokinetics and tissue distribution for highly efficient delivery of novel therapeutic agents and imaging agents. This project aims to image liver metastasis development and localization of KC in order to design an in silico model for administration of therapies and use a physical modeling process to optimize the properties of nanocarriers. Additionally, this project aims to refine, design, and evaluate biocompatibility of nanovectors for delivery of therapeutic and contrast agents for treatment of liver metastases, and to determine therapeutic and imaging efficacy of co-delivery of gold nanoparticles and cytotoxic agents from rationally designed targeted multi-stage nanovectors in in-vivo models of liver metastases.

Public Health Relevance

This project strives to image the development and progression of liver metastasis produced by colorectal cancers in orthotopic animal models and to investigate the efficiency of treatment through in silico models. A better understanding of the biology of liver metastasis will allow development of novel treatment modalities using nanotechnology, which should greatly impact public health by the elimination of liver metastasis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA143837-07
Application #
8755650
Study Section
Special Emphasis Panel (ZCA1-SRLB-9)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
7
Fiscal Year
2014
Total Cost
$600,660
Indirect Cost
$192,778
Name
Methodist Hospital Research Institute
Department
Type
DUNS #
185641052
City
Houston
State
TX
Country
United States
Zip Code
77030
Kojic, M; Milosevic, M; Kojic, N et al. (2018) Mass release curves as the constitutive curves for modeling diffusive transport within biological tissue. Comput Biol Med 92:156-167
Koay, Eugene J; Lee, Yeonju; Cristini, Vittorio et al. (2018) A Visually Apparent and Quantifiable CT Imaging Feature Identifies Biophysical Subtypes of Pancreatic Ductal Adenocarcinoma. Clin Cancer Res 24:5883-5894
Mu, Chaofeng; Wu, Xiaoyan; Zhou, Xinyu et al. (2018) Chemotherapy Sensitizes Therapy-Resistant Cells to Mild Hyperthermia by Suppressing Heat Shock Protein 27 Expression in Triple-Negative Breast Cancer. Clin Cancer Res 24:4900-4912
Amer, Ahmed M; Zaid, Mohamed; Chaudhury, Baishali et al. (2018) Imaging-based biomarkers: Changes in the tumor interface of pancreatic ductal adenocarcinoma on computed tomography scans indicate response to cytotoxic therapy. Cancer 124:1701-1709
Koay, Eugene J; Hall, William; Park, Peter C et al. (2018) The role of imaging in the clinical practice of radiation oncology for pancreatic cancer. Abdom Radiol (NY) 43:393-403
Martinez, Jonathan O; Molinaro, Roberto; Hartman, Kelly A et al. (2018) Biomimetic nanoparticles with enhanced affinity towards activated endothelium as versatile tools for theranostic drug delivery. Theranostics 8:1131-1145
Mai, Junhua; Li, Xin; Zhang, Guodong et al. (2018) DNA Thioaptamer with Homing Specificity to Lymphoma Bone Marrow Involvement. Mol Pharm 15:1814-1825
Krzykawska-Serda, Martyna; Agha, Mahdi S; Ho, Jason Chak-Shing et al. (2018) Chemotherapy and Radiofrequency-Induced Mild Hyperthermia Combined Treatment of Orthotopic Pancreatic Ductal Adenocarcinoma Xenografts. Transl Oncol 11:664-671
Tang, Chad; Hobbs, Brian; Amer, Ahmed et al. (2018) Development of an Immune-Pathology Informed Radiomics Model for Non-Small Cell Lung Cancer. Sci Rep 8:1922
Wang, Feng; Xia, Xiaojun; Yang, Chunying et al. (2018) SMAD4 Gene Mutation Renders Pancreatic Cancer Resistance to Radiotherapy through Promotion of Autophagy. Clin Cancer Res 24:3176-3185

Showing the most recent 10 out of 255 publications