Fisherduckworth0064

Armed CART19 and armed activated T cells (ATC) showed comparable specific cytotoxicity that ranged between 10 and 90% against breast, pancreatic, ovarian, prostate, and lung cancer cell lines at 101 E/T ratio. Serial killing (repeated killing) by HER2Bi-armed CART19 ranged between 80 and 100% at 101 E/T ratio against MCF-7 cells up to 19 days (up to 4th round of repeated killing) measured by a real-time cell analysis without CART19 becoming exhausted. Conclusions HER2Bi- or EGFRBi-armed CART19 exhibited specific cytotoxicity against multiple HER2+/EGFR+/CD19- tumor targets in overnight and long-term serial killing assays. CART19 showed improved survival and were resistant to exhaustion after prolonged repeated exposure to tumor cells.Purpose In mCRC, disease dynamics may play a critical role in the understanding of long-term outcome. We evaluated depth of response (DpR), time to DpR, and post-DpR survival as relevant endpoints. Methods We analyzed DpR by central review of computer tomography images (change from baseline to smallest tumor diameter), early tumor shrinkage (≥ 20% reduction in tumor diameter at first reassessment), time to DpR (study randomization to DpR-image), post-DpR progression-free survival (pPFS = DpR-image to tumor progression or death), and post-DpR overall survival (pOS = DpR-image to death) with special focus on BRAF status in 66 patients and primary tumor site in 86 patients treated within the VOLFI-trial, respectively. Results BRAF wild-type (BRAF-WT) compared to BRAF mutant (BRAF-MT) patients had greater DpR (- 57.6% vs. - 40.8%, p = 0.013) with a comparable time to DpR [4.0 (95% CI 3.1-4.4) vs. 3.9 (95% CI 2.5-5.5) months; p = 0.8852]. pPFS was 6.5 (95% CI 4.9-8.0) versus 2.6 (95% CI 1.2-4.0) months in favor of BRAF-WT patients (HR 0.24 (95% CI 0.11-0.53); p less then 0.001). This transferred into a significant difference in pOS [33.6 (95% CI 26.0-41.3) vs. 5.4 (95% CI 5.0-5.9) months; HR 0.27 (95% CI 0.13-0.55); p less then 0.001]. Similar observations were made for patients stratified for primary tumor site. Conclusions BRAF-MT patients derive a less profound treatment response compared to BRAF-WT patients. The difference in outcome according to BRAF status is evident after achievement of DpR with BRAF-MT patients hardly deriving any further disease control beyond DpR. Our observations hint towards an aggressive tumor evolution in BRAF-MT tumors, which may already be molecularly detectable at the time of DpR.Purpose Sorafenib is an oral tyrosine kinase inhibitor (TKI) and first-line treatment option for advanced hepatocellular carcinoma (HCC). Preliminary evidence indicates proton pump inhibitors (PPI) may affect the absorption of TKIs through decreased gut dissolution. This study aims to evaluate the impact of PPI use on the survival outcomes of advanced HCC patients treated with sorafenib. Methods The study was a secondary analysis of individual-participant data from the phase III clinical trial NCT00699374. Cox proportional hazard analysis was used to evaluate the association between baseline PPI use and survival outcomes. Overall survival (OS) was the primary outcome with progression-free survival (PFS) secondary. Results In a cohort of 542 advanced HCC patients initiating sorafenib treatment, 122 were concomitantly using a PPI at baseline. No significant associations between baseline PPI use and OS were identified on univariable (HR [95% CI]; 1.01 [0.80-1.28], P = 0.93) and adjusted (1.10 [0.82-1.41], P = 0.62) analysis. Furthermore, no significant associations between baseline PPI use and PFS were identified on univariable (0.96 [0.76-1.21], P = 0.73) and adjusted (1.11 [0.86-1.44], P = 0.41) analysis. Conclusion In a large high-quality dataset, PPI use was not observed to compromise the survival outcomes of advanced HCC patients initiated on sorafenib.Background The objective of this study was to compare the hyperemic myocardial blood flow (MBF) and myocardial flow reserve (MFR) obtained with dobutamine to those of dipyridamole in patients referred for myocardial perfusion imaging (MPI) using 82Rb positron emission tomography. Methods One hundred and fifty-six patients who underwent a 82Rb PET MPI study with dobutamine stress were included. A matching cohort of patients who underwent a 82Rb PET MPI study with dipyridamole stress was created, accounting for sex, age, history of coronary artery disease (CAD), prior revascularization, CAD risk factors, body mass index, and MPI interpretation. learn more Results Global rest MBF (median [interquartile range] 0.84 [0.64-1.00] vs 0.69 [0.59-0.85]), stress MBF (2.36 [1.73-3.08] vs 1.66 [1.25-2.06]), MFR (2.75 [2.19-3.64] vs 2.29 [1.78-2.84]), and corrected MFR (2.85 [2.14-3.64] vs 2.20 [1.65-2.75]) were all significantly higher (P less then 0.0001) in the dobutamine cohort compared to the dipyridamole cohort. Conclusion The results of this study suggest that dobutamine produces higher MBF compared to dipyridamole in a representative population referred to nuclear cardiology laboratories.Hearing is considered the primary sensory modality of cetaceans and enables their vital life functions. Information on the hearing sensitivity variability within a species obtained in a biologically relevant wild context is fundamental to evaluating potential noise impact and population-relevant management. Here, non-invasive auditory evoked-potential methods were adopted to describe the audiograms (11.2-152 kHz) of a group of four wild Yangtze finless porpoises (Neophocaena asiaeorientalis asiaeorientalis) during a capture-and-release health assessment project in Poyang Lake, China. All audiograms presented a U shape, generally similar to those of other delphinids and phocoenids. The lowest auditory threshold (51-55 dB re 1 µPa) was identified at a test frequency of 76 kHz, which was higher than that observed in aquarium porpoises (54 kHz). The good hearing range (within 20 dB of the best hearing sensitivity) was from approximately 20 to 145 kHz, and the low- and high-frequency hearing cut-offs (threshold > 120 dB re l μPa) were 5.6 and 170 kHz, respectively. Compared with aquarium porpoises, wild porpoises have significantly better hearing sensitivity at 32 and 76 kHz and worse sensitivity at 54, 108 and 140 kHz. The audiograms of this group can provide a basis for better understanding the potential impact of anthropogenic noise.