ABSTRACT
Massive swelling of the tongue can occur after posterior fossa and craniofacial surgery. Several hypotheses have been proposed to explain the occurrence of such severe postoperative macroglossia, but this phenomenon is still poorly understood. Severe postoperative macroglossia can be a life-threatening condition due to upper airway obstruction. Three cases of severe postoperative macroglossia that occurred after cervical spine, craniofacial, and posterior fossa surgical procedures are reported here. These cases required specialized maxillofacial management and a prolonged stay in the intensive care unit. Causal factors involved in this condition are reported, in order to highlight appropriate prevention and treatment options adapted to the management of paediatric patients. An overview of the current literature on severe postoperative macroglossia in paediatric populations is also provided.
Subject(s)
Cervical Vertebrae/surgery , Cranial Fossa, Posterior/surgery , Craniofacial Abnormalities/surgery , Macroglossia/etiology , Macroglossia/therapy , Postoperative Complications/etiology , Postoperative Complications/therapy , Adolescent , Child , Female , Humans , Infant , MaleABSTRACT
PTEN phosphatase acts as a tumor suppressor by negatively regulating the phosphoinositide 3-kinase (PI3K) signaling pathway. It is unclear which downstream components of this pathway are necessary for oncogenic transformation. In this report we show that transformed cells of PTEN(+/-) mice have elevated levels of phosphorylated Akt and activated p70/S6 kinase associated with an increase in proliferation. Pharmacological inactivation of mTOR/RAFT/FRAP reduced neoplastic proliferation, tumor size, and p70/S6 kinase activity, but did not affect the status of Akt. These data suggest that p70/S6K and possibly other targets of mTOR contribute significantly to tumor development and that inhibition of these proteins may be therapeutic for cancer patients with deranged PI3K signaling.
Subject(s)
Phosphoric Monoester Hydrolases/deficiency , Protein Kinase Inhibitors , Protein Kinases , Ribosomal Protein S6 Kinases/metabolism , Tumor Suppressor Proteins , Alleles , Animals , Base Sequence , Cell Transformation, Neoplastic/drug effects , DNA Primers/genetics , Female , Humans , Mice , Mice, Knockout , PTEN Phosphohydrolase , Phosphatidylinositol 3-Kinases/metabolism , Phosphoric Monoester Hydrolases/genetics , Signal Transduction , Sirolimus/analogs & derivatives , Sirolimus/pharmacology , TOR Serine-Threonine Kinases , Uterine Neoplasms/drug therapy , Uterine Neoplasms/genetics , Uterine Neoplasms/metabolism , Uterine Neoplasms/pathologyABSTRACT
PTEN is a tumor suppressor that antagonizes phosphatidylinositol-3 kinase (PI3K) by dephosphorylating the D3 position of phosphatidylinositol (3,4,5)-triphosphate (PtdIns-3,4,5-P3). Given the importance of PTEN in regulating PtdIns-3,4,5-P3 levels, we used Affymetrix GeneChip arrays to identify genes regulated by PTEN. PTEN expression rapidly reduced the activity of Akt, which was followed by a G(1) arrest and eventually apoptosis. The gene encoding insulin receptor substrate 2 (IRS-2), a mediator of insulin signaling, was found to be the most induced gene at all time points. A PI3K-specific inhibitor, LY294002, also upregulated IRS-2, providing evidence that it was the suppression of the PI3K pathway that was responsible for the message upregulation. In addition, PTEN, LY294002, and rapamycin, an inhibitor of mammalian target of rapamycin, caused a reduction in the molecular weight of IRS-2 and an increase in the association of IRS-2 with PI3K. Apparently, PTEN inhibits a negative regulator of IRS-2 to upregulate the IRS-2-PI3K interaction. These studies suggest that PtdIns-3,4,5-P3 levels regulate the specific activity and amount of IRS-2 available for insulin signaling.
