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Currently available databases of detailed gene expression in different vascular cell types from the mouse brain could be used to explore a possible integrative model.
ATTRACTION-2 demonstrated that nivolumab improved overall survival (OS) vs placebo in patients with advanced gastric cancer treated with ≥ 2 chemotherapy regimens. However, its long-term efficacy and outcome of treatment beyond progression (TBP) with nivolumab have not been clarified.
The 3-year follow-up data were collected. A subset analysis was performed to explore the efficacy of TBP by assessing postprogression survival (PPS) after the first event of disease progression.
Overall, 493 patients were randomized (21) to receive nivolumab (n = 330) or placebo (n = 163). With a median follow-up of 38.5 (range 36.1-47.5) months, OS of the nivolumab group was significantly longer compared to the placebo group (median 5.3 vs 4.1months; 3-year survival rate, 5.6% vs 1.9%; hazard ratio [HR], 0.62 [95% confidence interval (CI) 0.50-0.75], P < 0.0001). The median OS of responders (n = 32) who achieved complete response or partial response was 26.7months and the 3-year survival rate was 35.5% in the nivolumab group. Overall, 109 patients in the nivolumab group and 37 patients in the placebo group received TBP. PPS tended to be longer in the nivolumab group vs placebo group (median 5.8 vs 4.5months; HR [95% CI], 0.69 [0.47-1.01], P = 0.057). In contrast, PPS was similar between both treatment groups in non-TBP patients (median 2.3 vs 2.2months; HR 0.90, P = 0.42).
Long-term efficacy of nivolumab was confirmed at the 3-year follow-up, and a survival benefit of TBP with nivolumab was suggested. Biomarkers for selecting patients suitable for TBP with nivolumab should be identified in the future.
Long-term efficacy of nivolumab was confirmed at the 3-year follow-up, and a survival benefit of TBP with nivolumab was suggested. Biomarkers for selecting patients suitable for TBP with nivolumab should be identified in the future.
The aim of this study was to identify serum miRNAs that discriminate early gastric cancer (EGC) samples from non-cancer controls using a large cohort.
This retrospective case-control study included 1417 serum samples from patients with EGC (seen at the National Cancer Center Hospital in Tokyo between 2008 and 2012) and 1417 age- and gender-matched non-cancer controls. The samples were randomly assigned to discovery and validation sets and the miRNA expression profiles of whole serum samples were comprehensively evaluated using a highly sensitive DNA chip (3D-Gene
) designed to detect 2565 miRNA sequences. Diagnostic models were constructed using the levels of several miRNAs in the discovery set, and the diagnostic performance of the model was evaluated in the validation set.
The discovery set consisted of 708 samples from EGC patients and 709 samples from non-cancer controls, and the validation set consisted of 709 samples from EGC patients and 708 samples from non-cancer controls. The diagnostic EGC index was constructed using four miRNAs (miR-4257, miR-6785-5p, miR-187-5p, and miR-5739). In the discovery set, a receiver operating characteristic curve analysis of the EGC index revealed that the area under the curve (AUC) was 0.996 with a sensitivity of 0.983 and a specificity of 0.977. In the validation set, the AUC for the EGC index was 0.998 with a sensitivity of 0.996 and a specificity of 0.953.
A novel combination of four serum miRNAs could be a useful non-invasive diagnostic biomarker to detect EGC with high accuracy. A multicenter prospective study is ongoing to confirm the present observations.
A novel combination of four serum miRNAs could be a useful non-invasive diagnostic biomarker to detect EGC with high accuracy. A multicenter prospective study is ongoing to confirm the present observations.Most clotting factors were initially discovered as agents functionally deficient in the plasmas of rare patients with hereditary coagulation disorders. During 1940s to 1960s, many factors were named by different investigators after the name of the patient who lacked a new factor. Consequently, there were the same factors with different names. To avoid confusion, the International Committee on the nomenclature of clotting factors was founded and discussed the identity or non-identity of clotting factors by specialists. There remain, however, several factors that were not officially authorized. We attempt to review some of these factors that seem to be not identical with any known clotting factors.High-dose methotrexate (MTX) is widely used for the treatment of hematological malignancies. Despite the application of routine supportive care measures, such as intensive fluid hydration and urine alkalinization, nephrotoxicity is still a problem. The present study aimed to evaluate the risk factors for MTX-induced nephrotoxicity. We retrospectively reviewed 88 patients who received a regimen consisting of high-dose MTX (1000 mg/m2) and cytosine arabinoside between 2006 and 2018. Nephrotoxicity (≥ grade 2) was observed in 11 patients. AG-1024 mouse Nephrotoxicity was observed only in patients with a high MTX concentration. Other than the MTX concentration, the serum uric acid level and urine pH at day 1 were associated with nephrotoxicity. A multivariate analysis revealed that urine pH was an independent risk factor for MTX-induced nephrotoxicity. Urine pH less then 7.0 at day 1 was a significant risk factor for nephrotoxicity (odds ratio, 8.05; 95% confidence interval 1.95-33.3) and was also a predictor of delayed MTX elimination at 72 h after injection. Among pre-treatment factors, a low serum calcium level predicted urine pH less then 7.0 at day 1. In conclusion, the present study suggests that low urine pH at day 1 is an independent risk factor for MTX-induced nephrotoxicity.
Physical therapies have been recommended as crucial components in Parkinson's disease (PD) rehabilitation.
The study aims to examine the effectiveness of a new dance-physiotherapy combined intervention, called DArT method, in mild PD patients.
A prospective, randomized, single-blind, controlled pilot trial was conducted on 38 mild PD patients under dopaminergic therapy. The intervention consisted in an add-on protocol the control group received 1 h of conventional physiotherapy followed by 1 h of conventional physiotherapy each day, 3 times a week, for 5 weeks. The experimental group received 1 h of conventional physiotherapy followed by 1 h of dance class each day, 3 times a week, for 5 weeks. The week before and after the training period, patients were assessed for motor, cognitive, emotional, and sensory components of PD, with MDS-UPDRS-III as primary outcome measure.
DArT method was associated with a 2.72-point reduction in the post-treatment MDS-UPDRS-III total score compared to control group (95% CI - 5.
My Website: https://www.selleckchem.com/products/ag-1024-tyrphostin.html
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