000			nab a22 7a 4500
999			_c16836 _d16836
003			PC16836
005			20220505131527.0
008			220505b xxu||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_91974 _aLombera Romero, Federico _eCardiología
100			_93035 _aFernández, María S _eCardiología
100			_9433 _aSepúlveda Sánchez, Juan Manuel _eOncología Médica
245	0	0	_aCardiac Safety of TGF-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Cancer Patients in a First-in-Human Dose Study. _h[artículo]
260			_bCardiovascular toxicology, _c2015
300			_a15(4):309-23.
500			_aFormato Vancouver: Kovacs RJ, Maldonado G, Azaro A, Fernández MS, Romero FL, Sepulveda Sánchez JM et al. Cardiac Safety of TGF-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Cancer Patients in a First-in-Human Dose Study. Cardiovasc Toxicol. 2015 Oct;15(4):309-23.
501			_aPMID: 25488804 PMCID: PMC4575352
504			_aContiene 36 referencias
520			_aTransforming growth factor-beta (TGF-β) 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-β 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-β 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-β inhibitor LY2157299 did not detect medically relevant cardiac toxicity and hence supports the evaluation of LY2157299 in future clinical trials.
710			_9119 _aServicio de Cardiología
710			_9303 _aServicio de Oncología Médica
856			_uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575352/ _yAcceso libre
942			_2ddc _cART _n0