Sirolimus treatment of severe PTEN hamartoma tumor syndrome: case report and in vitro studies
| Autor: | Andreas Laner, Frank Kowalzik, Adrian Viehweger, Franziska Wilhelm, Susanne Schuster, Gordian L. Schmid, Norman Händel, Wieland Kiess, Fred-P. Zepp, Wolfgang Hirsch, Jürgen Kratzsch, Franziska Kässner, Antje Körner, Sven Starke, Holm H. Uhlig, Antje Garten |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Lipomatosis
In Vitro Techniques Drug therapy Hamartoma Paediatrics PTEN PHTS PI3K AKT mTOR medicine Humans Tensin PTEN ddc:610 Protein kinase B PI3K/AKT/mTOR pathway Sirolimus biology business.industry Infant Newborn PTEN Phosphohydrolase Infant Lipoma medicine.disease Child Preschool Pediatrics Perinatology and Child Health Cancer research biology.protein Thymus hyperplasia Hamartoma Syndrome Multiple business medicine.drug |
| Zdroj: | Pediatric Research. 75:527-534 |
| ISSN: | 1530-0447 0031-3998 |
| Popis: | Background: Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is caused by germ line mutations in the PTEN gene. Symptoms include cancer pre- disposition, immune deviations, and lipomas/lipomatosis. No causal standard therapy is available. We describe a therapeutic attempt with the mammalian target of rapamycin (mTOR) inhibitor sirolimus for a PHTS patient suffering from thymus hyperplasia and lipomatosis. We furthermore assessed the in vitro effects of sirolimus and other inhibitors on lipoma cells of the patient. Methods: The patient underwent clinical and blood examinations and whole-body magnetic resonance imaging to assess tumor sizes. Lipoma cells of the patient were incubated with inhibitors of the phosphoinositide3-kinase (PI3K)/AKT/ mTOR signaling pathway to analyze the effects on proliferation, adipocyte differentiation, and survival in vitro. Results: Sirolimus treatment improved somatic growth and reduced thymus volume. These effects diminished over the treatment period of 19 mo. Sirolimus decreased lipoma cell proliferation and adipocyte differentiation in vitro but did not cause apoptosis. PI3K and AKT inhibitors induced apoptosis significantly. Conclusion: Sirolimus treatment led to an improvement of the patient’s clinical status and a transient reduction of the thymus. Our in vitro findings point to PI3K and AKT inhibitors as potential treatment options for patients with severe forms of PHTS. |
| Databáze: | OpenAIRE |
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