BACKGROUND Regorafenib is an oral small-molecule multikinase inhibitor approved in third or later line of treatment for patients with metastatic colorectal cancer(mCRC).Regorafenib has shown significant benefits in ov...
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BACKGROUND Regorafenib is an oral small-molecule multikinase inhibitor approved in third or later line of treatment for patients with metastatic colorectal cancer(mCRC).Regorafenib has shown significant benefits in overall survival and progression free survival in two phase III trials compared to placebo in patients with mCRC who had progressed on previous *** To identify an immune profile that might specifically correlate with the outcome in patients treated with *** Blood samples were collected from 17 patients before treatment with regorafenib and from 6 healthy *** proteins evaluated(TNF-α,TGF-β,VEGF,CCL-2,CCL-4,and CCL-5)were selected on the basis of their roles in angiogenesis and colorectal cancer *** We found that TNF-αbasal level was significantly higher in mCRC patients compared to healthy *** Responder(NR)patients showing progression of disease(n=12)had higher basal level of TGF-β,TNF-α,VEGF,CCL-2 and CCL-5 compared to Responder(R)patients(complete response CR,n=1;partial response PR,n=1;Stable Disease SD,n=3).On the contrary,plasma basal level of CCL-4 was higher in R compared to NR *** values of TGF-βand TNF-αnegatively correlated with progression free *** These results suggest a cytokine signature potentially able to discriminate between R and NR patients to treatment with regorafenib.
BACKGROUND Non-clear cell(ncc)metastatic renal-cell carcinoma(RCC)has dismal results with standard systemic therapies and a generally worse prognosis when compared to its clear-cell *** systemic combination therapies ...
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BACKGROUND Non-clear cell(ncc)metastatic renal-cell carcinoma(RCC)has dismal results with standard systemic therapies and a generally worse prognosis when compared to its clear-cell *** systemic combination therapies have emerged for metastatic RCC(mRCC),but the pivotal phase III trials excluded patients with nccRCC,which constitute about 30%of metastatic RCC *** To provide a piece of real-life evidence on the use of pazopanib in this patient *** The present study is a multicenter retrospective observational analysis aiming to assess the activity,efficacy,and safety of pazopanib as first-line therapy for advanced nccRCC patients treated in a real-life *** Overall,48 patients were *** the median follow-up of 40.6 mo,the objective response rate was 27.1%,the disease control rate was 83.3%,and the median progression-free survival and overall survival were 12.3(95%confidence interval[CI]:3.6-20.9)and 27.7(95%CI:18.2-37.1)mo,*** 3 adverse events occurred in 20%of patients,and no grade 4 or 5 toxicities were *** Pazopanib should be considered as a good first-line option for metastatic RCC with variant histology.
Real-time simulation-based validation plays an essential role in the early stage development of electric traction *** high-fidelity real-time simulation relies on the accurate modeling of the power electronics and mot...
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Real-time simulation-based validation plays an essential role in the early stage development of electric traction *** high-fidelity real-time simulation relies on the accurate modeling of the power electronics and motors and usually represents the nonlinear characteristics as many as possible while obeying the computing time *** this paper,an artificial neural network(ANN)aided modeling approach is proposed for the field-programmable gate array(FPGA)-based real-time simulation to deal with the nonlinearities in permanent magnet synchronous motor(PMSM)and its *** the help of the ANN,the switches power losses,and the PMSM nonlinear flux linkage and electromagnetic torque can be *** electro-thermal model of inverters and the finite element analysis(fea)-based PMSM model are thus enabled in the FPGA-based real-time simulation,which can significantly improve the performances of the real-time simulation-based test bench.A two-level inverter fed PMSM drive system is modeled using the ANN-aided modeling approach and simulated in the National Instrument PXIe FlexRIO FPGA real-time *** accuracy and effectiveness of the proposed approaches are tested and validated by comparing the results with the offline simulation tools.
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