2 research outputs found
Myocardial Dysfunction in Elderly Patients Admitted with Non-Cardiac Diagnosis in Intensive Care Unit
No full textBackground and Objectives: The diagnosis of acute coronary syndromes can be challenging in patients admitted with the non-cardiac disease to the Intensive Care Unit (ICU). The study aimed to determine the clinical profile of critically ill elderly patients developing myocardial injury who were admitted to ICU for non-cardiac diagnosis.
Materials and Methods: The retrospective study subjects are 130 patients admitted to the medical ICU. Within 24 hours of admission to ICU a detailed history, a 12 lead ECG, CK-MB, Cardiac troponin T was done and as required based on ECG findings and development of clinical symptoms.
Results: Our study showed that 35 out of 130 patients developed acute myocardial injury. 13 out of 35 patients who had myocardial injury had a fatal outcome. The prevalence of hypertension, diabetes mellitus, history of CVA, history of IHD and COPD reached statistical significance (p<0.001) between the two groups of patients who developed myocardial injury and who did not develop a myocardial injury. In patients with multiple comorbidities, the presence of factors like hypoxia, hypotension and the use of vasopressors increases the risk of mortality.
Conclusion: All elderly patients who are hospitalized with or without multiple comorbidities with an acute form of stressors must be evaluated aggressively for precipitants and adequately treated to prevent myocardial injury
MELK-Dependent FOXM1 Phosphorylation is Essential for Proliferation of Glioma Stem Cells
No full textGlioblastoma multiforme (GBM) is a life-threatening brain tumor. Accumulating evidence suggests that eradication of glioma stem-like cells (GSCs) in GBM is essential to achieve cure. The transcription factor FOXM1 has recently gained attention as a master regulator of mitotic progression of cancer cells in various organs. Here, we demonstrate that FOXM1 forms a protein complex with the mitotic kinase MELK in GSCs, leading to phosphorylation and activation of FOXM1 in a MELK kinase-dependent manner. This MELK-dependent activation of FOXM1 results in a subsequent increase in mitotic regulatory genes in GSCs. MELK-driven FOXM1 activation is regulated by the binding and subsequent trans-phosphorylation of FOXM1 by another kinase PLK1. Using mouse neural progenitor cells (NPCs), we found that transgenic expression of FOXM1 enhances, while siRNA-mediated gene silencing diminishes neurosphere formation, suggesting that FOXM1 is required for NPC growth. During tumorigenesis, FOXM1 expression sequentially increases as cells progress from NPCs, to pretumorigenic progenitors and GSCs. The antibiotic Siomycin A disrupts MELK-mediated FOXM1 signaling with a greater sensitivity in GSC compared to neural stem cell. Treatment with the first-line chemotherapy agent for GBM, Temozolomide, paradoxically enriches for both FOXM1 (+) and MELK (+) cells in GBM cells, and addition of Siomycin A to Temozolomide treatment in mice harboring GSC-derived intracranial tumors enhances the effects of the latter. Collectively, our data indicate that FOXM1 signaling through its direct interaction with MELK regulates key mitotic genes in GSCs in a PLK1-dependent manner and thus, this protein complex is a potential therapeutic target for GBM. STEM Cells 2013;31:1051-1063.sponsorship: We thank Z. Fu for kindly providing the FOXM1 vectors and constructive discussion for this study. We also thank Dr. Mark Drew for technical support for the FACS experiments and Amy Haseley for assistance in the luciferase-based promoter assay experiments. This work was supported by the Start-up budget for I. Nakano at the Ohio State University, Department of Neurological Surgery, the American Cancer Society Grant for I. Nakano (MRSG-08-108-01), and the National Science Foundation Grant for M. Beullens (grant G.0686.10). L. M. L. C. is a St. Baldrick's Foundation Scholar and is supported by a Sontag Foundation Distinguished Scientist Award. R. W. S. is supported by grants from the National Institutes of Health (NIH), CA148629, GM087798, NS037704, ES019498, GM099213. H. I. K. is supported by the NIH, NS0525630. I.N. is also supported by Vincent J. Sgro/The American Brain Tumor Association and National Brain Tumor Foundation. (Ohio State University, Department of Neurological Surgery, American Cancer Society|MRSG-08-108-01, National Science Foundation|G.0686.10, Sontag Foundation Distinguished Scientist Award, National Institutes of Health (NIH)|CA148629, National Institutes of Health (NIH)|GM087798, National Institutes of Health (NIH)|NS037704, National Institutes of Health (NIH)|ES019498, National Institutes of Health (NIH)|GM099213, National Institutes of Health (NIH)|NS0525630, Vincent J. Sgro/The American Brain Tumor Association, National Brain Tumor Foundation)status: Publishe
