PMID- 24366516
OWN - NLM
STAT- MEDLINE
DCOM- 20141117
LR  - 20161125
IS  - 1530-0447 (Electronic)
IS  - 0031-3998 (Linking)
VI  - 75
IP  - 4
DP  - 2014 Apr
TI  - Sirolimus treatment of severe PTEN hamartoma tumor syndrome: case report and in 
      vitro studies.
PG  - 527-34
LID - 10.1038/pr.2013.246 [doi]
AB  - BACKGROUND: Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) 
      is caused by germ line mutations in the PTEN gene. Symptoms include cancer 
      predisposition, 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 phosphoinositide-3-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.
FAU - Schmid, Gordian L
AU  - Schmid GL
AD  - 1] Hospital for Children & Adolescents, Department of Women and Child Health, 
      Center for Pediatric Research Leipzig, University of Leipzig, Leipzig, Germany 
      [2] Leipzig University Medical Center, IFB Adiposity Diseases, Leipzig, Germany.
FAU - Kassner, Franziska
AU  - Kassner F
AD  - Hospital for Children & Adolescents, Department of Women and Child Health, Center 
      for Pediatric Research Leipzig, University of Leipzig, Leipzig, Germany.
FAU - Uhlig, Holm H
AU  - Uhlig HH
AD  - John Radcliffe Hospital, Translational Gastroenterology Unit and Children's 
      Hospital, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, 
      UK.
FAU - Korner, Antje
AU  - Korner A
AD  - 1] Hospital for Children & Adolescents, Department of Women and Child Health, 
      Center for Pediatric Research Leipzig, University of Leipzig, Leipzig, Germany 
      [2] Leipzig University Medical Center, IFB Adiposity Diseases, Leipzig, Germany.
FAU - Kratzsch, Jurgen
AU  - Kratzsch J
AD  - Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, 
      University of Leipzig, Leipzig, Germany.
FAU - Handel, Norman
AU  - Handel N
AD  - Hospital for Children & Adolescents, Department of Women and Child Health, Center 
      for Pediatric Research Leipzig, University of Leipzig, Leipzig, Germany.
FAU - Zepp, Fred-P
AU  - Zepp FP
AD  - Department of Paediatrics, University Medical Center, Johannes 
      Gutenberg-University Mainz, Mainz, Germany.
FAU - Kowalzik, Frank
AU  - Kowalzik F
AD  - Department of Paediatrics, University Medical Center, Johannes 
      Gutenberg-University Mainz, Mainz, Germany.
FAU - Laner, Andreas
AU  - Laner A
AD  - Medical Genetics Center, Munich, Germany.
FAU - Starke, Sven
AU  - Starke S
AD  - Hospital for Children & Adolescents, Department of Women and Child Health, Center 
      for Pediatric Research Leipzig, University of Leipzig, Leipzig, Germany.
FAU - Wilhelm, Franziska K
AU  - Wilhelm FK
AD  - 1] Hospital for Children & Adolescents, Department of Women and Child Health, 
      Center for Pediatric Research Leipzig, University of Leipzig, Leipzig, Germany 
      [2] Leipzig University Medical Center, IFB Adiposity Diseases, Leipzig, Germany.
FAU - Schuster, Susanne
AU  - Schuster S
AD  - Hospital for Children & Adolescents, Department of Women and Child Health, Center 
      for Pediatric Research Leipzig, University of Leipzig, Leipzig, Germany.
FAU - Viehweger, Adrian
AU  - Viehweger A
AD  - Department of Paediatric Radiology, University of Leipzig, Leipzig, Germany.
FAU - Hirsch, Wolfgang
AU  - Hirsch W
AD  - Department of Paediatric Radiology, University of Leipzig, Leipzig, Germany.
FAU - Kiess, Wieland
AU  - Kiess W
AD  - Hospital for Children & Adolescents, Department of Women and Child Health, Center 
      for Pediatric Research Leipzig, University of Leipzig, Leipzig, Germany.
FAU - Garten, Antje
AU  - Garten A
AD  - Hospital for Children & Adolescents, Department of Women and Child Health, Center 
      for Pediatric Research Leipzig, University of Leipzig, Leipzig, Germany.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131223
PL  - United States
TA  - Pediatr Res
JT  - Pediatric research
JID - 0100714
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Child, Preschool
MH  - Hamartoma Syndrome, Multiple/*drug therapy/genetics
MH  - Humans
MH  - In Vitro Techniques
MH  - Infant
MH  - Infant, Newborn
MH  - PTEN Phosphohydrolase/*genetics
MH  - Sirolimus/*therapeutic use
EDAT- 2013/12/25 06:00
MHDA- 2014/11/18 06:00
CRDT- 2013/12/25 06:00
PHST- 2013/04/25 00:00 [received]
PHST- 2013/09/14 00:00 [accepted]
PHST- 2013/12/25 06:00 [entrez]
PHST- 2013/12/25 06:00 [pubmed]
PHST- 2014/11/18 06:00 [medline]
AID - pr2013246 [pii]
AID - 10.1038/pr.2013.246 [doi]
PST - ppublish
SO  - Pediatr Res. 2014 Apr;75(4):527-34. doi: 10.1038/pr.2013.246. Epub 2013 Dec 23.