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Beighley Adam Glynn Ryan Scullen Tyler Mathkour Mansour Werner Cassidy Berry John F. Carr Christopher Abou-Al-Shaar Hussam Aysenne Aimee Nerva John D. Dumont Aaron S. 《Neurosurgical review》2021,44(5):2511-2522
Neurosurgical Review - Aneurysmal subarachnoid hemorrhage (aSAH) is an emergent condition requiring rapid intervention and prolonged monitoring. There are few recommendations regarding the... 相似文献
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Andrew J. Yee Parameswaran Hari Raffaella Marcheselli Anuj K. Mahindra Diana D. Cirstea Tyler A. Scullen Jill N. Burke Scott J. Rodig Teru Hideshima Jacob P. Laubach Irene M. Ghobrial Robert L. Schlossman Nikhil C. Munshi Kenneth C. Anderson Edie A. Weller Paul G. Richardson Noopur S. Raje 《British journal of haematology》2014,166(3):401-409
Everolimus, an oral mammalian target of rapamycin (mTOR) inhibitor, has been studied in multiple myeloma (MM) but lacks significant single agent activity. Based on preclinical studies showing synergistic activity of mTOR inhibitors with lenalidomide, we studied the combination of lenalidomide and everolimus in relapsed or refractory MM in a phase I clinical trial. We assessed patient samples using gene expression, Western blotting and immunohistochemistry to probe the mTOR pathway. Twenty‐six patients were evaluable for toxicity. Dose‐limiting toxicities included grade 4 neutropenia and thrombocytopenia. The maximum tolerated dose was lenalidomide 15 mg and everolimus 5 mg for 21 d with a 7 d rest period. Grade 3/4 adverse events included thrombocytopenia (35%) and neutropenia (42%). The overall response rate was 65% (1 complete response + 4 partial response + 10 minimal response). The median progression‐free survival was 5·5 months and median overall survival was 29·5 months. Biomarker data demonstrated downregulation of phosphorylated p70S6K. Gene expression profiling suggested activation of mTOR in responders versus non‐responders. The combination of lenalidomide and everolimus was well tolerated with predictable toxicities and showed responses in a heavily pretreated population. When confirmed with larger patient numbers, this analysis may guide patient selection for future clinical trials of mTOR inhibition in MM. 相似文献
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