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Do I Araujo ES Kalil RK Bacchini P Bertoni F Unni KK Park YK 《Pathology, research and practice》2007,203(3):127-134
Ewing sarcoma is a highly malignant tumor of bone preferentially arising in children and young adults. Its 5-year survival rate is only 50% despite the use of multimodal therapeutic approaches, requiring a search for new therapeutic targets and the development of novel therapeutic modalities. KIT and PDGFRs are type III receptor tyrosine kinases, and activating mutations in c-kit (which encodes KIT) and PDGFRs have been reported as oncogenic events in many malignancies. Imatinib is a selective inhibitor of KIT, PDGFR, and ABL tyrosine kinase activity and exerts different anti-tumor effects according to the regions of mutations in c-kit and PDGFR genes. Thus, we evaluated the immunohistochemical expression of KIT protein and the mutational status of exons 9, 11, 13, and 17 of the c-kit gene, exons 12 and 18 of the PDGFRA gene, and exon 12 of the PDGFRB gene in 71 formalin-fixed, paraffin-embedded Ewing sarcomas to increase our understanding of the potential, if any, of imatinib treatment for this malignancy. Of the 71 samples, 27 (38%) were immunohistochemically positive for KIT; however, activating mutations in c-kit were found in only 2 of 71 Ewing sarcomas (2.6%) within exon 9. No activating mutations in the PDGFRA and PDGFRB genes were found, but pleomorphism was identified in exon 18 of the PDGFRA gene. Our results for KIT protein expression agree with those of previous studies. This is the largest series of c-kit mutational analysis in Ewing sarcoma to date, and the results definitively show that c-kit activating mutations are not coincident with KIT protein expression in Ewing sarcoma in most samples. These findings imply other mechanisms for KIT activity and leave open the question of whether imatinib would be efficacious in the treatment of Ewing sarcoma. 相似文献
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Henry C M'Baïlara K Desage A Gard S Misdrahi D Vieta E 《Journal of affective disorders》2007,101(1-3):35-41
BACKGROUND: DSM-IV criteria for mixed states may be too restrictive and may actually exclude patients who do not meet the full criteria for a manic and depressive state. Using this DSM-IV definition, many patients who are considered depressed may have mixed features, which can explain why some bipolar depressive states can worsen with antidepressants and can be improved by mood stabilizers or atypical antipsychotics. A dimensional approach not exclusively focused on the tonality of affect would help to define a broader entity of mixed states. The aim of this study was to apply a dimensional model to bipolar episodes and to assess the overlap between the groups defined using this model and using categorical diagnosis. METHOD: We assessed 139 DSM-IV acutely ill bipolar I patients with MAThyS (Multidimensional Assessment of Thymic States by Henry et al. in press), a scale that assesses five quantitative dimensions exploring excitatory and inhibition processes, and that is not focused on tonality of mood but on emotional reactivity. We studied the relationship between clusters defined by statistical analyses and DSM-IV bipolar mood states. RESULTS: This study showed the existence of three clusters. Cluster 1 was characterized by an inhibition in all dimensions and corresponded to the depressive cluster (more than 90% of patients met the criteria for DSM-IV Major Depressive Episode (MDE)). Cluster 2 showed a general excitation and was mainly DSM-IV manic or hypomanic patients (90%). Cluster 3 (Mixed) was more complex and the diagnosis included MDE (56%) in most of the cases associated with manic or hypomanic symptoms, mixed states (18%) defined by DSM-IV criteria, and manic or hypomanic states (25%). Emotional reactivity was relevant to distinguish Cluster 1 (Depressive), exhibiting emotional hypo-reactivity, from Cluster 2 (Manic) and 3 (Mixed), characterized by emotional hyper-reactivity. Sadness was reported equally in all three clusters. CONCLUSION: A dimensional approach using the concept of emotional reactivity seems appropriate to define a broad mixed state entity in patients who would be diagnosed with MDE according to DSM-IV. Further studies are needed to test the relevance of this model in therapeutic strategies. 相似文献
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Ana González-Pinto Purificación López-Peña Cristina Bermúdez-Ampudia Eduard Vieta Mónica Martinez-Cengotitabengoa 《European neuropsychopharmacology》2018,28(12):1351-1359
To critically examine the effectiveness of lithium in preventing depressive symptoms (mixed and depressive episodes) in real life settings, taking into account adherence to drug treatment and its implications for the clinical costs of the disease. Overall, 72 patients with bipolar disorder initially treated with lithium carbonate were included and followed-up for 10 years. Patients were assessed every 8 weeks for morbidity and alcohol/drug consumption. Patients with good adherence to lithium had fewer episodes with depressive features than poor adherers (B?=?2.405, p?=?0.046) and also fewer manic and hypomanic episodes (B?=?2.572; p?<?0.001), after controlling for confounders. Time to relapse into a depressive or mixed episode and into a manic or hypomanic episode was shorter in patients with poor adherence. The costs of the 1.95?±?2.38 (mean?±?standard deviation) admissions of adherent patients through the 10 years of follow-up were €10,349, while the costs of the 6.25?±?4.92 admissions of non-adherent patients were €44,547. In clinical practice settings, long-term lithium salts seem to have a preventive effect on depressive symptoms. 相似文献
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Huebner Lucas Schroeder Ines Kraft Eduard Gutmann Marcus Biebl Johanna Klamt Amrei Christin Frey Jana Warmbein Angelika Rathgeber Ivanka Eberl Inge Fischer Uli Scharf Christina Schaller Stefan J. Zoller Michael 《Der Anaesthesist》2022,71(10):795-800
Die Anaesthesiologie - Bei etwa 43?% aller Überlebenden der Intensivmedizin wird ein erworbenes Syndrom an Muskelschwäche beobachtet, welches Überleben und Lebensqualität... 相似文献
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Davide Carino MD Alejandro Fernández-Cisneros MD Marta Hernández-Meneses MD Elena Sandoval MD FECTS Jaume Llopis MD PhD Carlos Falces MD PhD José M. Miró MD PhD Eduard Quintana MD PhD FECTS Grup d'Estudi d'Endocarditis Infecciosa de l'Hospital Clínic de Barcelona 《Journal of cardiac surgery》2020,35(11):3034-3040