Ultrasonic standing waves can be used to generate forces on particles within a fluid. Such forces have a number of potential applications in microfluidic devices. This paper describes a device that provides filtration on a microfluidic scale. It is microfabricated and uses ultrasound in the megahertz frequency range to concentrate particles at a node within the flow. It offers the possibility of a functional equivalent of a centrifugal separator for microfluidic systems. It is constructed using silicon and Pyrex, and hence is compatible with established microfabrication techniques. The modelling, design, fabrication and control of the device are discussed.
Retinoic acid-related orphan receptor C (RORC) is a member of the nuclear orphan receptor family and performs critical regulatory functions in cell proliferation, metastasis, and chemoresistance in various types of malignant tumors. Here we showed that expression of RORC is lost in tumor tissues of bladder cancer patients. Enhanced expression of RORC suppressed cell proliferation and glucose metabolism and increased cisplatin-induced apoptosis in vitro and in vivo. RORC bound the promoter region of programmed death ligand-1 (PD-L1) and negatively regulated PD-L1 expression. PD-L1 directly interacted with integrin b6 (ITGB6) and activated the ITGB6/FAK signaling pathway. RORC prevented the nuclear translocation of STAT3 via suppression of the PD-L1/ITGB6 signaling pathway, which further inhibited bladder cell proliferation and glucose metabolism and increased cisplatin-induced apoptosis. These findings reveal that RORC regulates bladder cancer cell proliferation, glucose metabolism, and chemoresistance by participating in the PD-L1/ITGB6/STAT3 signaling axis. Moreover, this new understanding of PD-L1 signaling may guide the selection of therapeutic targets to prevent tumor recurrence. Significance: These findings suggest that RORC-mediated regulation of a PD-L1/ITGB6/FAK/STAT3 signaling axis in bladder cancer provides several potential therapeutic targets to prevent tumor progression.
Background:An intravenous formulated extract of the venom of the wild toad Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider, huachansu, is currently used in China for the treatment of lung, liver, pancreatic, and colorectal cancers. We performed a randomised, single-blinded, phase II clinical study of huachansu plus gemcitabine versus placebo plus gemcitabine in patients with locally advanced and/or metastatic pancreatic adenocarcinomas.Methods:Patients with tissue-proven locally advanced and/or metastatic pancreatic adenocarinoma were randomly assigned to receive either gemcitabine 1000 mg m−2 on days 1, 8, and 15 with huachansu 20 ml m−2 daily for 21 days (arm A) or placebo (arm B); treatment cycles were 28 days in length. Primary end point was 4-month progression-free overall survival (PFS); secondary end points were objective radiographical response rate (ORR), time to progression (TTP), and toxicity.Results:A total of 80 subjects were enrolled; 76 patients were evaluable (received at least 1 week therapy). Median overall survival was 160 days for arm A and 156 days for arm B (P=0.339); ORR was 9 and 3% in arms A and B, respectively (P=0.332), median TTP was 98 and 115 days, respectively (P=0.825); the median 4-month PFS was 99 and 98 days, respectively (P=0.679).Conclusion:Huachansu when combined with gemcitabine did not improve the outcome of patients with locally advanced and/or metastatic pancreatic cancer.
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