ABSTRACT
Phosphatidylinositol 5-monophosphate (PtdIns5P), one of the latest phosphoinositides discovered, has been suggested to play important cellular functions. Here, we report the presence of higher levels of this lipid in cells expressing the oncogenic tyrosine kinase nucleophosmin anaplastic lymphoma kinase (NPM-ALK), a chimeric protein found in the large majority of anaplastic large cell lymphomas (ALCLs). In addition, we describe that a pool of PtdIns5P is located in the membrane extensions characteristic of NPM-ALK-transformed cells. Finally, we show that the increase of PtdIns5P is controlled by the kinase PIKfyve, which is known for its role in vesicular trafficking. These data suggest for the first time a role of PtdIns5P and PIKfyve in oncogenesis, potentially linking intracellular trafficking to cancer.
Subject(s)
Cell Transformation, Neoplastic/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol Phosphates/metabolism , Protein-Tyrosine Kinases/metabolism , Animals , Cell Transformation, Neoplastic/genetics , Humans , Mice , NIH 3T3 Cells , Phosphatidylinositol Phosphates/analysis , Protein-Tyrosine Kinases/geneticsABSTRACT
OBJECTIVE: According to certain learned societies, acute pancreatitis mortality should not exceed 10%. The aim of our work was to review the etiology, severity and mortality of acute pancreatitis in a prospective series of patients admitted to a regional university hospital in France, using standardised collection of data assessing the medico-surgical habits in the management of acute pancreatitis. METHODS: From February to September 1999, 86 patients (54 men and 32 women with a mean age of 58.5 years) were admitted for 88 episodes of acute pancreatitis. Data was collected from all the patients on admission and permitted measurement of the severity and prognosis scores and the study of the etiology, complications and management of the latter and the mortality with acute pancreatitis. RESULTS: Ranson's score was a mean of 2.4. Balthazar's score was superior or equal to D in 45% of cases. The respective prevalence of lithiasis, alcoholism, tumors, others or undetermined was of 41%, 37.5%, 7%, 5.5% and 9%. Acute pancreatitis was severe (multi organ failure, pseudo-cyst, systemic or necrotic infection and occlusive syndrome) in 32% of cases. Complications were: infection (22%), pseudo-cyst (14%), pleural effusion (12.5%) and occlusive syndrome (3.5%). Fever of more than 38.5 degrees C was noted in more than half of the patients. The median duration of hospitalisation was of 11 days (range: 1-86 days). Global hospital mortality was of 13.6% (12/88), and of 43% (12/28) in cases of severe acute pancreatitis. Six deaths occurred within the first 8 days of acute pancreatitis, and 6 after 8 days. Seven deaths (59%) were due to multi organ failure, 4 (33%) to infectious causes and one to another cause. CONCLUSION: The standardized collection of clinical and progressive data used in this study permitted assessment of the medico-surgical habits in a regional university hospital.
