scholarly journals Standardization procedure for plasma biomarker analysis in rat models of epileptogenesis: Focus on circulating microRNAs

Epilepsia ◽  
2017 ◽  
Vol 58 (12) ◽  
pp. 2013-2024 ◽  
Author(s):  
Erwin A. van Vliet ◽  
Noora Puhakka ◽  
James D. Mills ◽  
Prashant K. Srivastava ◽  
Michael R. Johnson ◽  
...  
2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 81-81 ◽  
Author(s):  
Daisuke Takahari ◽  
Takeru Wakatsuki ◽  
Tetsuo Mashima ◽  
Keisho Chin ◽  
Takashi Ichimura ◽  
...  

81 Background: Ramucirumab, anti-VEGFR2 receptor antibody, showed significantly improved survivals of gastric cancer in the second line with paclitaxel or single use. Recently we reported early elevation of plasma VEGF-A was associated with shorter survival as a preliminary result. We will report the results of final analysis. Methods: Patients with advanced gastric cancer who received ramucirumab combined with paclitaxel or single use were enrolled. Plasma samples were collected at pre-treatment and day 8 after administration. Nine kinds of plasma biomarker involved in angiogenesis, VEGF-A, C, D, PlGF, VEGFR1, 2, Angiopoietin 1, stromal cell derived factor-1α (SDF1α), and Neuropirin-1, were measured by means of ELISA. Patients were dichotomized by optimal cut-off value. Univariate and multivariate analysis were done by Cox proportion hazard model. Results: Forty-one patients were enrolled. Thirty-nine patients (95.1%) received ramucirumab with paclitaxel. Plasma VEGF-A, D, PlGF, and VEGFR2 levels were significantly increased one week after administration compared with baseline levels, while plasma VEGFR1 and NRP1levels were significantly decreased. Median PFS and OS were 5.6 (95% CI 4.66-6.54) and 9.8 (95% CI 5.41-14.19) months, respectively. In univariate analysis, higher baseline SDF1α and PlGF levels resulted in shorter OS with HR 2.71 95% CI 1.23-6.00, p =0.013 for SDF1α and HR 2.78 95% CI 1.16-6.65, p =0.022 for PlGF. Higher D8 VEGF-A was associated with shorter PFS with HR 2.77 95% CI 1.39-5.51, p =0.004. While higher D8 VEGF-D was associated with better PFS with HR 0.39 95% CI 0.20-0.77, p =0.007. In multivariate analysis, higher baseline SDF1α and PlGF were independent negative prognostic factor for OS with HR 2.45 95% CI 1.10-5.42, p =0.028 for SDF1α and HR 2.48 95% CI 1.03-5.96, p =0.043. With respect to PFS, higher D8 VEGF-A was also independent negative prognostic factor with HR 2.32 95% CI 1.13-4.77, p =0.022, while higher D8 VEGF-D was favorable predictor for PFS with HR 0.47 95% CI 0.23-0.96, p =0.038. Conclusions: Higher base line SDF1α and PlGF levels may be negative prognostic marker. While early VEGF-A and D elevation after ramucirumab administration may be predictive marker of ramucirumab.


2014 ◽  
Vol 30 (10) ◽  
pp. S207-S208
Author(s):  
H. Yogasundaram ◽  
B.N. Putko ◽  
I. Paterson ◽  
R.B. Thompson ◽  
A. Khan ◽  
...  

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 72-72 ◽  
Author(s):  
Daisuke Takahari ◽  
Takeru Wakatsuki ◽  
Tetsuo Mashima ◽  
Takashi Ichimura ◽  
Keisho Chin ◽  
...  

72 Background: Ramucirumab, anti-VEGFR2 receptor antibody, showed significantly improved survivals of gastric cancer in the second line with paclitaxel or single use; however, no validated biomarker has been available until today. The aim of this study is 1) to reveal the dynamics of plasma biomarkers, 2) to assess the associations between these baseline levels or dynamics and efficacy. Methods: Plasma samples were collected at three points: base line, day 8, and after disease progression. Nine kinds of plasma biomarker involved in angiogenesis were measured by means of ELISA. Progression-free survival (PFS) was estimated using Kaplan-Meier methods and compared using the log-rank test. Comparisons of plasma biomarker levels were performed using Mann-Whitney-U test. Results: Samples were collected from 35 patients. Among them, 25 patients were evaluated when analyzed and 6 patients showed disease progression at the first evaluation. In VEGF-A and PlGF, plasma biomarker levels of day 8 were dramatically elevated in all patients; Day8/ baseline ratios were 18.1 folds in VEGF-A and 19.3 folds in PlGF. On the other hand, Day8/ baseline ratio of VEGFR1 and NRP1 were 0.7 and 0.8, respectively. The others appeared to show variable change at day 8. In survival analysis, lower than median Day8/ baseline ratios of VEGF-A were significantly associated with longer PFS with 6.3 months in < median vs. 2.4 months in ≥ median (p = 0.004). In addition, patients with disease progression at the first evaluation by CT showed higher Day8/ baseline ratios of VEGF-C, Angiopoietin 1, and lower baseline NRP1 levels than those of patients with non-disease progression. Conclusions: Dramatic changes of biomarker levels at day 8 were observed among patients in each biomarker. These changes in VEGF-A, C, and Angiopoietin-1 may be candidate predictive marker of ramucirumab in Japanese patients with gastric cancer.


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