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10.1007/s12012-014-9297-4 http://scihub22266oqcxt.onion/10.1007/s12012-014-9297-4 C4575352!4575352 !25488804     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25488804 &cmd=llinks): Failed to open stream: HTTP request failed! 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Cardiac Safety of TGF-? Receptor I Kinase Inhibitor LY2157299 Monohydrate in Cancer Patients in a First-in-Human Dose Study |pdf=|usr=}}{{25488804 }} gab.com Text Cardiac Safety of TGF- Receptor I Kinase Inhibitor LY2157299 Monohydrate in Cancer Patients in a First-in-Human Dose Study JO: Cardiovasc Toxicol http://www.kidney.de/pget.php?&tw=1&pmid=25488804 #FOAvip Transforming growth factor-beta (TGF-?) signaling plays an important role in the fetal development of cardiovascular organs and in the repair mechanisms of the heart. Hence, inhibitors of the TGF-? signaling pathway require a careful identification of a safe therapeutic window and a comprehensive monitoring of the cardiovascular system. Seventy-nine cancer patients (67 glioma and 12 solid tumor) enrolled in a first-in-human dose study and received the TGF-? inhibitor LY2157299 monohydrate (LY2157299) as monotherapy (n = 53) or in combination with lomustine (n = 26). All patients were monitored using 2D echocardiography/color and Spectral Doppler (2D Echo with Doppler) every 2 months, monthly electrocardiograms, thorax computer tomography scans every 6 months, and monthly serum brain natriuretic peptide (BNP), troponin I, cystatin C, high-sensitivity C-reactive protein (hs-CRP). Administration of LY2157299 was not associated with medically relevant cardiovascular toxicities, including patients treated ?6 months (n = 13). There were no increases of troponin I, BNP, or hs-CRP or reduction in cystatin C levels, which may have been considered as signs of cardiovascular injury. Blood pressure was generally stable during treatment. Imaging with echocardiography/Doppler showed an increase in mitral and tricuspid valve regurgitation by two grades of severity in only one patient with no concurrent clinical symptoms of cardiovascular injury. Overall, this comprehensive cardiovascular monitoring for the TGF-? inhibitor LY2157299 did not detect medically relevant cardiac toxicity and hence supports the evaluation of LY2157299 in future clinical trials. Twit Text FOAVip Cardiac Safety of TGF- Receptor I Kinase Inhibitor LY2157299 Monohydrate in Cancer Patients in a First-in-Human Dose Study ????Cardiovasc Toxicol http://www.kidney.de/pget.php?&tw=1&pmid=25488804 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25488804 #FOAvip English Wikipedia <ref>{{Cite pmid|25488804 }}</ref> Cardiac Safety of TGF-? Receptor I Kinase Inhibitor LY2157299 Monohydrate in Cancer Patients in a First-in-Human Dose Study #MMPMID25488804 Kovacs RJ ; Maldonado G ; Azaro A ; Fernández MS ; Romero FL ; Sepulveda-Sánchez JM ; Corretti M ; Carducci M ; Dolan M ; Gueorguieva I ; Cleverly AL ; Pillay NS ; Baselga J ; Lahn MM Cardiovasc Toxicol 2015[Oct]; 15 (4 ): 309-23 PMID25488804 show ga Transforming growth factor-beta (TGF-?) signaling plays an important role in the fetal development of cardiovascular organs and in the repair mechanisms of the heart. Hence, inhibitors of the TGF-? signaling pathway require a careful identification of a safe therapeutic window and a comprehensive monitoring of the cardiovascular system. Seventy-nine cancer patients (67 glioma and 12 solid tumor) enrolled in a first-in-human dose study and received the TGF-? inhibitor LY2157299 monohydrate (LY2157299) as monotherapy (n = 53) or in combination with lomustine (n = 26). All patients were monitored using 2D echocardiography/color and Spectral Doppler (2D Echo with Doppler) every 2 months, monthly electrocardiograms, thorax computer tomography scans every 6 months, and monthly serum brain natriuretic peptide (BNP), troponin I, cystatin C, high-sensitivity C-reactive protein (hs-CRP). Administration of LY2157299 was not associated with medically relevant cardiovascular toxicities, including patients treated ?6 months (n = 13). There were no increases of troponin I, BNP, or hs-CRP or reduction in cystatin C levels, which may have been considered as signs of cardiovascular injury. Blood pressure was generally stable during treatment. Imaging with echocardiography/Doppler showed an increase in mitral and tricuspid valve regurgitation by two grades of severity in only one patient with no concurrent clinical symptoms of cardiovascular injury. Overall, this comprehensive cardiovascular monitoring for the TGF-? inhibitor LY2157299 did not detect medically relevant cardiac toxicity and hence supports the evaluation of LY2157299 in future clinical trials. |Adult [MESH] |Aged [MESH] |Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use [MESH] |Biomarkers/blood [MESH] |Blood Pressure/drug effects [MESH] |Echocardiography, Doppler [MESH] |Electrocardiography [MESH] |Female [MESH] |Heart Diseases/blood/chemically induced/diagnostic imaging [MESH] |Humans [MESH] |Lomustine/administration & dosage [MESH] |Male [MESH] |Middle Aged [MESH] |Neoplasms/*drug therapy/enzymology/pathology [MESH] |Prospective Studies [MESH] |Protein Kinase Inhibitors/*administration & dosage/adverse effects [MESH] |Protein Serine-Threonine Kinases/*antagonists & inhibitors/metabolism [MESH] |Pyrazoles/*administration & dosage/adverse effects [MESH] |Quinolines/*administration & dosage/adverse effects [MESH] |Receptor, Transforming Growth Factor-beta Type I [MESH] |Receptors, Transforming Growth Factor beta/*antagonists & inhibitors/metabolism [MESH] |Risk Assessment [MESH] |Risk Factors [MESH] |Signal Transduction/drug effects [MESH] |Spain [MESH] |Time Factors [MESH] |Treatment Outcome [MESH]Cardiac Safety of TGF-? Receptor I Kinase Inhibitor LY2157299 Monohydr(epmc).pdf DeepDyve Pubget Overpricing