The goal of this proposal is define the role of vascularization in metastasis and to identify the role of pathophysiological insults in the metastatic process. The investigations will be performed using magnetic resonance imaging (MRI) and spectroscopy (MRS) to examine orthotopic and subcutaneous human prostate cancer models in SCID mice and isolated human prostate cancer cells. The proposed studies are designed to test the hypotheses that: (1) cell lines preselected for higher invasive and metastatic potential will induce and exhibit a higher vascular volume or permeability or both; and (2) a significant fraction of the histologically identified vessels are not functional and the resultant hostile environment (low pH, oxygen, and glucose) increases the invasive behavior of a sub-population of cells.
The aims of the in vivo studies are: (a) to characterize vasculature in terms of vascular volume and permeability using high resolution MRI for comparison with immunohistochemical measurements of Factor VIII and vascular endothelial growth factor (VEGF) expression; and (b) increase either the tumor vascularization by mixing the injection inoculum with dextran beads loaded with basis fibroblast growth factor (bFGF) or both tumor vascularization and permeability by mixing the inoculum with dextran beads loaded with VEGF.
The aim of the cell studies is to develop a """"""""Metabolic Boyden Chamber"""""""" for MR studies of metabolism and invasion of isolated and perfused cells to determine the role of the lactate concentration, pH and oxygen tension in invasion.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA073850-02
Application #
2683694
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Menkens, Anne E
Project Start
1997-06-11
Project End
2001-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Bharti, Santosh K; Mironchik, Yelena; Wildes, Flonne et al. (2018) Metabolic consequences of HIF silencing in a triple negative human breast cancer xenograft. Oncotarget 9:15326-15339
Chen, Zhihang; Krishnamachary, Balaji; Penet, Marie-France et al. (2018) Acid-degradable Dextran as an Image Guided siRNA Carrier for COX-2 Downregulation. Theranostics 8:1-12
Penet, Marie-France; Kakkad, Samata; Pathak, Arvind P et al. (2017) Structure and Function of a Prostate Cancer Dissemination-Permissive Extracellular Matrix. Clin Cancer Res 23:2245-2254
Krishnamachary, Balaji; Stasinopoulos, Ioannis; Kakkad, Samata et al. (2017) Breast cancer cell cyclooxygenase-2 expression alters extracellular matrix structure and function and numbers of cancer associated fibroblasts. Oncotarget 8:17981-17994
Shah, Tariq; Wildes, Flonne; Kakkad, Samata et al. (2016) Lymphatic endothelial cells actively regulate prostate cancer cell invasion. NMR Biomed 29:904-11
Jin, Jiefu; Krishnamachary, Balaji; Mironchik, Yelena et al. (2016) Phototheranostics of CD44-positive cell populations in triple negative breast cancer. Sci Rep 6:27871
Penet, Marie-France; Jin, Jiefu; Chen, Zhihang et al. (2016) Magnetic Resonance Imaging and Spectroscopy in Cancer Theranostic Imaging. Top Magn Reson Imaging 25:215-221
Winnard Jr, Paul T; Bharti, Santosh K; Penet, Marie-France et al. (2016) Detection of Pancreatic Cancer-Induced Cachexia Using a Fluorescent Myoblast Reporter System and Analysis of Metabolite Abundance. Cancer Res 76:1441-50
Penet, Marie-France; Chen, Zhihang; Mori, Noriko et al. (2016) Magnetic Resonance Spectroscopy of siRNA-Based Cancer Therapy. Methods Mol Biol 1372:37-47
Chen, Zhihang; Penet, Marie-France; Krishnamachary, Balaji et al. (2016) PSMA-specific theranostic nanoplex for combination of TRAIL gene and 5-FC prodrug therapy of prostate cancer. Biomaterials 80:57-67

Showing the most recent 10 out of 63 publications