PTHrP Treatment Fails to Rescue Bone Defects Caused by Hedgehog Pathway Inhibition in Young Mice
| Autor: | Tom Curran, Jessica M.Y. Ng, Jillian L. Brechbiel |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Indian hedgehog Cellular differentiation Biology Toxicology Article Pathology and Forensic Medicine Mice Chondrocytes Pregnancy Internal medicine medicine Animals Hedgehog Proteins Basal cell carcinoma Growth Plate Molecular Targeted Therapy Molecular Biology Hedgehog Medulloblastoma Parathyroid hormone-related protein Parathyroid Hormone-Related Protein Cancer Cell Differentiation Cell Biology medicine.disease biology.organism_classification Hedgehog signaling pathway Endocrinology Female Signal Transduction |
| Zdroj: | Toxicologic Pathology. 39:478-485 |
| ISSN: | 1533-1601 0192-6233 |
| DOI: | 10.1177/0192623311399788 |
| Popis: | The advent of molecular targeted therapies offers the hope of therapeutic advance in the fight against cancer. However, this hope is tempered by recent findings that certain targeted therapies may have unique side effects. The Hedgehog (HH) pathway is a potential target for treatment of several cancers, including basal cell carcinoma and a subset of medulloblastoma. Recent clinical trials in adults have shown responses to HH pathway inhibition in both basal cell carcinoma and medulloblastoma. However, concerns have been raised about the use of HH pathway inhibitors in children because of the role the HH pathway plays in development. Indeed, young mice treated with the HH pathway inhibitor HhAntag developed severe bone defects, including premature differentiation of chondrocytes, thinning of cortical bone, and fusion of the growth plate. In an effort to lessen the severity of bone defects caused by HhAntag, we treated young mice simultaneously with HhAntag and parathyroid hormone–related protein (PTHrP), which functions downstream of Indian Hedgehog to maintain chondrocytes in a proliferative state. The results show that whereas treatment with PTHrP causes a significant increase in trabecular bone, it does not prevent fusion of the growth plate induced by HhAntag. |
| Databáze: | OpenAIRE |
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