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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Schally, Andrew V. Jaeger, Laura B. Banks, William A. Varga, Jozsef L. |
| Description | Author Affiliation: Jaeger LB ( Department of Pharmacological and Physiological Sciences, Division of Geriatrics, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.); |
| Abstract | Hypothalamic growth hormone (GH)-releasing hormone (GHRH) stimulates the synthesis and release of GH from the pituitary gland. GHRH and its mRNA are also found in human cancers of the breast, ovary, prostate, lung, and other tumors, suggesting that GHRH is also a tumor growth factor. Various studies show that GHRH antagonists have antiproliferative effects in many tumor models; however, glioblastomas were examined only recently. Previous studies have demonstrated that s.c. administration of GHRH antagonist (JV-1-36) inhibited growth of s.c. U-87MG human glioblastomas and increased survival of nude mice with orthotopic implants of glioblastomas. Although treatment with JV-1-36 reduced tumorigenicity, it is not known whether peripherally administered GHRH antagonists can cross the blood-brain barrier. Brain endothelial cells joined by tight junctions form the blood-brain barrier, a 'barrier' between the general circulation and the CNS. In this study, we administered a GHRH antagonist (JV-1-42) and showed that, after i.v. injection, iodinated JV-1-42 (131I-JV-1-42) enters the brain intact at a rate of 0.8514 mocrol/g per min with a serum half-life of 12.2 min. A one-site binding hyperbolic model indicated that the maximal percent of i.v. dose taken up per gram of brain was 0.41%. Coinjection of unlabeled JV-1-42 indicated that the transport from blood to brain is not saturable; however, transport from brain to blood is saturable and involves P-glycoprotein. Taken together, these results demonstrate that i.v.-administered 131I-JV-1-42 readily crosses the blood-brain barrier and accumulates in the brain. This finding indicates that GHRH antagonists could provide a potential treatment for malignant glioblastomas. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 35 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Blood-Brain Barrier Brain Neoplasms Drug Therapy Metabolism Gonadotropin-Releasing Hormone Antagonists & Inhibitors Animals Blood Glioblastoma Iodine Radioisotopes Mice Mice, Nude Neoplasm Transplantation Transplantation, Heterologous Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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