"Firefly" Mechanism Makes Cancer Studies More Efficient, Less Expensive
April 01, 2015
Bioluminescence measures response by multiple tumors to vascular disrupting agents
The mechanism that makes fireflies glow through a process called bioluminescence can be used to study tumor response to therapy as well, researchers have found. Led by Barjor Gimi, PhD of Dartmouth-Hitchcock's Norris Cotton Cancer Center and Ralph Mason, PhD from The University of Texas Southwestern Medical Center at Dallas with first author Li Liu, PhD, the team published the findings in their paper "Dynamic bioluminescence and fluorescence imaging of the effects of the antivascular agent Combretastatin-A4P (CA4P) on brain tumor xenografts," in Cancer Letters.
"By using a model of multiple tumors in the same animal, we established a platform for more efficient studies requiring fewer animals," explained Gimi. "Another benefit of the multiple tumors-same animal model is that it provides more consistency in interpreting results."
Bioluminescence has a major role in small animal research, and the technique has been widely applied in tumor models. The multiple tumor approach can also be used for high throughput screening of a vast range of anti-cancer drug therapies.
In this study, investigators used dynamic bioluminescence imaging to study the effects of a tumor vascular disrupting agent, provided by OXiGENE, known as CA4P on subcutaneous 9L rat brain tumor xenografts in mice. A single dose of CA4P induced rapid, temporary tumor vascular shutdown, as revealed by a rapid and reproducible decrease of light emission. The vasculature showed distinct recovery within 24 hours post therapy, and multiple tumors behaved similarly.
"The beauty of using bioluminescence is that it is relatively inexpensive, has no background signal, and has been validated against other imaging modalities," said Gimi.
Looking forward, the collaborators intend to pursue further investigation using combinatorial approaches where all the tumors in a single animal are subject to the same systemic vascular disrupting agent, followed by a second, local, and tailored treatment.
Barjor Gimi is an Associate Professor of Radiology and of Medicine at Dartmouth's Geisel School of Medicine. His work in cancer is facilitated by Dartmouth-Hitchcock's Norris Cotton Cancer Center where he is a member of the Cancer Imaging and Radiobiology Research Program.
"Dynamic bioluminescence and fluorescence imaging of the effects of the antivascular agent Combretastatin-A4P (CA4P) on brain tumor xenografts," was supported in part by funds from NIHR01 CA140674 and U24 CA126608, and facilitated by the Southwestern Small Animal Imaging and Live Cell Imaging Resources of the Harold C. Simmons Cancer Center through an NCI Cancer Center Support Grant, 1P30 CA142543. The Caliper IVIS Spectrum was purchased under NIH 1S10RR024757.
About Dartmouth-Hitchcock Norris Cotton Cancer Center
Norris Cotton Cancer Center combines advanced cancer research at Dartmouth and the Geisel School of Medicine with patient-centered cancer care provided at Dartmouth-Hitchcock Medical Center in Lebanon, NH, at Dartmouth-Hitchcock regional locations in Manchester, Nashua, and Keene, NH, and St. Johnsbury, VT, and at 12 partner hospitals throughout New Hampshire and Vermont. It is one of 41 centers nationwide to earn the National Cancer Institute's "Comprehensive Cancer Center" designation. Learn more about Norris Cotton Cancer Center research, programs, and clinical trials online at cancer.dartmouth.edu.
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