Alimentary TractRecombinant soluble transforming growth factor β type II receptor ameliorates radiation enteropathy in mice☆,☆☆
Section snippets
Production of soluble TβR-II:Fc fusion protein
The extracellular domain of the murine TβR-II was amplified from a murine lung complementary DNA library (Clontech, Palo Alto, CA) by polymerase chain reaction (PCR), and engineered to contain a 5' Not1 and a 3' Sal1 restriction site. The Fc region of murine immunoglobulin (Ig) G2a was amplified by PCR from a murine hybridoma and engineered to contain a 5' Sal1 restriction site and a 3' Not1 restriction site. The receptor and Fc fragments were purified, digested with the appropriate restriction
Results
Acute radiation-induced complications were similar in TβR-II:Fc–treated mice and IgG-treated controls. As expected, approximately 50% of the mice (11 in the TβR-II:Fc group, 14 in the IgG group) developed symptoms of severe toxicity and were killed before the scheduled observation time of 42 days. Animals that survived until the scheduled 6-week observation time point (10 TβR-II:Fc–treated and 8 IgG-treated) appeared normal and in no distress. Only sections from these animals were used to
Discussion
The risk of normal tissue injury limits the radiation dose that can be safely delivered to a tumor, and thereby its curability. Whereas acute normal tissue toxicity is generally a result of death of rapidly proliferating cells, delayed toxicity in many organs is characterized by progressive fibrosis and vascular sclerosis. Chronic intestinal radiation injury is a debilitating disorder, affects the quality of life in a large cohort of cancer survivors, and is an important obstacle to
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Address requests for reprints to: Martin Hauer-Jensen, M.D., Ph.D., Arkansas Cancer Research Center, 4301 West Markham, Slot 725, Little Rock, Arkansas 72205. e-mail: [email protected]; fax: (501) 686-7861.
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Supported by grant CA71382 from the National Institutes of Health.