Use my Search Websuite to scan PubMed, PMCentral, Journal Hosts and Journal Archives, FullText. Kick-your-searchterm to multiple Engines kick-your-query now !>

A dictionary by aggregated review articles of nephrology, medicine and the life sciences Your one-stop-run pathway from word to the immediate pdf of peer-reviewed on-topic knowledge.

10.1016/j.clml.2013.11.001 http://scihub22266oqcxt.onion/10.1016/j.clml.2013.11.001 C4096861!4096861 !24355079     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\24355079 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Clin+Lymphoma+Myeloma+Leuk 2014 ; 14 (3 ): 223-30 Nephropedia Template TP {{tp|p=24355079 |t=2014. A phase I and pharmacodynamic study of AT9283, a small-molecule inhibitor of aurora kinases in patients with relapsed/refractory leukemia or myelofibrosis |pdf=|usr=}}{{24355079 }} gab.com Text A phase I and pharmacodynamic study of AT9283, a small-molecule inhibitor of aurora kinases in patients with relapsed/refractory leukemia or myelofibrosis JO: Clin Lymphoma Myeloma Leuk http://www.kidney.de/pget.php?&tw=1&pmid=24355079 #FOAvip BACKGROUND: This study sought to identify the maximum tolerated dose (MTD) of AT9283, an inhibitor of Aurora kinases A and B, in patients with relapsed or refractory leukemias. Other endpoints included pharmacokinetics, safety and tolerability, pharmacodynamics, and preliminary evidence of efficacy. PATIENTS AND METHODS: AT9283 was administered as a continuous 72-hour infusion every 21 days. Doses were escalated by a standard 3 + 3 design. After the MTD for the 72-hour infusion was identified, infusion duration was increased incrementally to 96 hours and 120 hours. In total, 48 patients received ? 1 cycle of AT9283. Median age was 61 years (range, 22-86 years); 56% were men; 75% were diagnosed with AML; and 89% had received ? 3 (up to 16) prior lines of therapy. RESULTS: 324 mg/m(2)/72 h AT9283 was determined to be the MTD. Dose-limiting toxicities (DLTs) were myocardial infarction, hypertension, cardiomyopathy, tumor lysis syndrome, pneumonia, and multiorgan failure. Other AT9283-related toxicities (non-DLT) included myelosuppression, predominantly leukopenia and mucositis. Bone marrow blasts decreased ? 38% after AT9283 treatment in approximately one-third of patients with relapsed/refractory AML; however, this effect was transient and no objective responses were achieved, despite evidence of Aurora kinase B inhibition. Two patients with accelerated-phase chronic myeloid leukemia showed evidence of benefit, manifested as a cytogenetic response in 1 case; 1 patient completed 6 cycles of treatment. Exposure to AT9283 was generally dose proportional. CONCLUSION: AT9283 tolerability was strongly dose-dependent, with reversible myelosuppression predominating at lower doses and events such as cardiovascular toxicities manifesting at higher doses. Clinical trials with AT9283 are ongoing in alternative patient populations. Twit Text FOAVip A phase I and pharmacodynamic study of AT9283, a small-molecule inhibitor of aurora kinases in patients with relapsed/refractory leukemia or myelofibrosis ????Clin Lymphoma Myeloma Leuk http://www.kidney.de/pget.php?&tw=1&pmid=24355079 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24355079 #FOAvip English Wikipedia <ref>{{Cite pmid|24355079 }}</ref> A phase I and pharmacodynamic study of AT9283, a small-molecule inhibitor of aurora kinases in patients with relapsed/refractory leukemia or myelofibrosis #MMPMID24355079 Foran J ; Ravandi F ; Wierda W ; Garcia-Manero G ; Verstovsek S ; Kadia T ; Burger J ; Yule M ; Langford G ; Lyons J ; Ayrton J ; Lock V ; Borthakur G ; Cortes J ; Kantarjian H Clin Lymphoma Myeloma Leuk 2014[Jun]; 14 (3 ): 223-30 PMID24355079 show ga BACKGROUND: This study sought to identify the maximum tolerated dose (MTD) of AT9283, an inhibitor of Aurora kinases A and B, in patients with relapsed or refractory leukemias. Other endpoints included pharmacokinetics, safety and tolerability, pharmacodynamics, and preliminary evidence of efficacy. PATIENTS AND METHODS: AT9283 was administered as a continuous 72-hour infusion every 21 days. Doses were escalated by a standard 3 + 3 design. After the MTD for the 72-hour infusion was identified, infusion duration was increased incrementally to 96 hours and 120 hours. In total, 48 patients received ? 1 cycle of AT9283. Median age was 61 years (range, 22-86 years); 56% were men; 75% were diagnosed with AML; and 89% had received ? 3 (up to 16) prior lines of therapy. RESULTS: 324 mg/m(2)/72 h AT9283 was determined to be the MTD. Dose-limiting toxicities (DLTs) were myocardial infarction, hypertension, cardiomyopathy, tumor lysis syndrome, pneumonia, and multiorgan failure. Other AT9283-related toxicities (non-DLT) included myelosuppression, predominantly leukopenia and mucositis. Bone marrow blasts decreased ? 38% after AT9283 treatment in approximately one-third of patients with relapsed/refractory AML; however, this effect was transient and no objective responses were achieved, despite evidence of Aurora kinase B inhibition. Two patients with accelerated-phase chronic myeloid leukemia showed evidence of benefit, manifested as a cytogenetic response in 1 case; 1 patient completed 6 cycles of treatment. Exposure to AT9283 was generally dose proportional. CONCLUSION: AT9283 tolerability was strongly dose-dependent, with reversible myelosuppression predominating at lower doses and events such as cardiovascular toxicities manifesting at higher doses. Clinical trials with AT9283 are ongoing in alternative patient populations. |Adult [MESH] |Aged [MESH] |Aged, 80 and over [MESH] |Antineoplastic Agents/pharmacology/*therapeutic use [MESH] |Benzimidazoles/*therapeutic use [MESH] |Disease Progression [MESH] |Drug Administration Schedule [MESH] |Female [MESH] |Humans [MESH] |Leukemia/diagnosis/*drug therapy/*pathology [MESH] |Male [MESH] |Maximum Tolerated Dose [MESH] |Middle Aged [MESH] |Primary Myelofibrosis/diagnosis/*drug therapy/*pathology [MESH] |Protein Kinase Inhibitors/pharmacology/*therapeutic use [MESH] |Recurrence [MESH] |Treatment Outcome [MESH] |Urea/*analogs & derivatives/therapeutic use [MESH]A phase I and pharmacodynamic study of AT9283, a small-molecule inhibi(epmc).pdf DeepDyve Pubget Overpricing