Key Points• Single subcutaneous dosing of ACE910 has a linear PK profile, a half-life of 4 to 5 weeks, and FVIII-mimetic procoagulant activity in humans.• ACE910 at doses up to 1 mg/kg is well tolerated and has no notable adverse hypercoagulable effect in healthy Japanese and white adults.ACE910 is a recombinant humanized bispecific antibody that binds to activated factor IX and factor X and mimics the cofactor function of factor VIII (FVIII). This first-in-human study examined the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ACE910 in healthy male adults. A total of 40 Japanese and 24 white subjects were randomized to receive a single subcutaneous injection of ACE910 (Japanese: 0.001, 0.01, 0.1, 0.3, or 1 mg/kg; white: 0.1, 0.3, or 1 mg/kg; n 5 6 per dose group) or placebo (n 5 2 per dose group). ACE910 exhibited a linear PK profile and had a half-life of ∼4 to 5 weeks. In FVIIIneutralized plasma, ACE910 shortened activated partial thromboplastin time and increased peak height of thrombin generation in a dose-dependent manner. All adverse events were nonserious and did not lead to any subject's withdrawal. Neither clinical findings nor laboratory abnormalities indicating hypercoagulability were observed. Two of 48 subjects receiving ACE910 (1 Japanese and 1 white) were positive for anti-ACE910 antibodies (antidrug antibodies [ADAs]). One subject tested positive for ADAs both before and after ACE910 administration, whereas the other became ADA positive after receiving ACE910. The PK and PD profiles of ACE910 were similar in healthy Japanese and white subjects and suggest that ACE910 will be an effective and convenient prophylactic treatment of hemophilia A. This trial was registered at www

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: The recently developed technology of real-time cell analysis RTCA was designed to analyze cell migration and invasion in vitro. In this study, we investigated these cellular factors in oral squamous cell carcinomas OSCCs of the tongue and oor of the mouth with RTCA. We also examined the associated matrix metalloproteinases MMPs and integrins. We used the cell lines SCC-4 and SAS, which are human poorly differentiated OSCCs from the tongue, and HO-1-u-1, which are human poorly differentiated OSCCs from the oor of the mouth. Using RTCA, cell migration was assessed on fibronectin-coated CIM-Plates, and invasion was assessed on bronectin-and matrigel-coated CIM-Plates. SCC-4 cells demonstrated a high ability for cell migration and invasion compared with SAS and HO-1-u-1 cells. The SCC-4 cells also expressed high levels of MMP-9 and integrin 1 mRNA compared with SAS and HO-1-u-1 cells. The MMP inhibitor Marimastat blocked migration and invasion of all OSCCs. The ndings suggest that MMP-9 is associated with cell migration and invasion in OSCCs, and indicate that RTCA will be useful for analyzing the metastatic capability of OSCCs and developing more effective new drugs for this disease.

This new high-throughput NSAID determination method only requires a small tear amount (10 μl) and plasma volume (20 μl) and thus will be useful in clinical and toxicological analyses. Analytical results also showed the presence of ibuprofen and loxoprofen in the actual tears and plasma, which confirms the transition of NSAIDs from the tears to the plasma.

Background/Aim: There is an increasing use of immunotherapy for non-small cell lung cancer (NSCLC) patients. The present study analysed the effect of antibiotic use on the outcome of NSCLC patients undergoing treatment with anti-programmed cell death-1 (anti-PD-1) immunotherapy. Patients and Methods: This was a retrospective study of 69 NSCLC patients. Eighteen out of 69 patients received antibiotics within 21 days before or within 21 days after start of anti-PD-1 therapy. Results: Patients treated with anti-PD-1 antibodies receiving antibiotics had greatly decreased objective response rate (ORR), overall survival (OS) and progression-free survival (PFS) compared to those who did not use antibiotics. Multivariate analysis showed that antibiotic treatment of patients on anti-PD-1 antibody therapy was an independent negative predictive factor of PFS; however, it was not a significant independent predictive factor of OS. Conclusion: Use of antibiotics within 21 days before and after anti-PD-1 treatment initiation in patients with NSCLC strongly reduced OS and PFS, suggesting the two treatments should not be combined.Immunotherapy with anti-programmed cell death-1 (anti-PD-1) antibody has been only modestly successful in non-small cell lung cancer (NSCLC) (1). Thus, there is a critical need to identify more effective treatment strategies for anti PD-1 treatment of NSCLC.Specific intestinal bacteria have been reported to affect the immune system and therapeutic outcome of anti-PD-1 immunotherapy in NSCLC, melanoma, renal cell carcinoma (RCC) and urothelial carcinoma (UC) (2-5). Additionally, the diversity of bacterial flora may also affect the therapeutic outcome of anti-PD-1 immunotherapy (6).