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Immune checkpoint inhibitors (ICIs), such as nivolumab, play an essential role in non-small-cell lung cancer (NSCLC) treatment. Programmed death ligand-1 has been used as a predictive biomarker for the efficacy of ICI treatment in patients with NSCLC; however, its predictive value is considered insufficient. Therefore, there is an urgent need for better predictive biomarkers. The present study focused on the CD47 molecule, which is associated with macrophages and tumor immunity. The study aimed to investigate the association between CD47 single nucleotide polymorphism (SNP) and the therapeutic effect of nivolumab in patients with NSCLC. The CD47 SNP genotypes and clinical outcomes were retrospectively analyzed in 164 patients with NSCLC treated with nivolumab at Kyoto University Hospital (Kyoto, Japan). Patients with the G/G genotype of the CD47 SNP rs3804639 had significantly longer progression-free survival than those with the G/T or T/T genotypes [2.6 months vs. 2.1 months, hazard ratio (HR), 0.70; P=0.026]. Moreover, the G/G genotype of the CD47 SNP rs3804639 was associated with a significantly longer median overall survival than the G/T or T/T genotypes of the CD47 SNP rs3804639 (24.8 months vs. 12.0 months, HR, 0.64; P=0.021). In conclusion, CD47 polymorphism may be a novel predictive biomarker of nivolumab efficacy in patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]

A prototype surface-reaction-type pre-reacted glass-ionomer (S-PRG) filler containing root canal sealer (S-PRG sealer) exhibits bioactive potential by releasing multiple ions. This study explored the suppressive effects and modes of action of S-PRG sealer extracts on proinflammatory cytokine expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Expression of proinflammatory cytokines was evaluated by RT-qPCR and ELISA. Expression of phosphorylated nuclear factor-kappa B (p-NF-kB) p65 was evaluated by western blotting. S-PRG sealer extracts significantly downregulated mRNA expression levels of interleukin (IL)-1α, IL-6, and TNF-α in LPS-stimulated RAW264.7 cells; the extracts also reduced the levels of IL-6 protein and p-NF-kB. In order to verify that Zn2+ was responsible for downregulation of proinflammatory cytokine expression, N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) was used as a heavy metal chelator with strong affinity for Zn2+. These effects were mitigated by TPEN. The application of ZnCl2 reproduced the actions of S-PRG sealer extracts. These data suggest that S-PRG sealer has anti-inflammatory potential involving heavy metal ions such as Zn2+. [ABSTRACT FROM AUTHOR]

This study compared the cytocompatibilities of three methacrylate resin-based root canal sealers [MetaSEAL Soft (MSS), Hybrid Root SEAL (HRS), and Superbond Sealer (SBS)] in either freshly mixed or set conditions using the Kusa A1 osteoblastic cell line. The three sealers and an epoxy resin-based sealer (AH Plus; AHP) were extracted in culture medium; cell growth and osteogenic properties were analyzed. Cell adhesion on set sealers was analyzed with scanning electron microscopy. The respective extents of cell growth were as follows in freshly mixed and set sealer extracts: SBS>MSS>AHP>HRS and SBS=AHP>MSS>HRS. Light irradiation of MSS and HRS increased the cell growth of set sealer extracts. Set SBS, MSS, and AHP did not alter expression of osteogenic genes or formation of mineralized nodules. Attached cells were observed only on SBS. In conclusion, the four sealers exhibited varying degrees of compatibility to osteoblasts; SBS and HRS were the most and least compatible, respectively. [ABSTRACT FROM AUTHOR]

Crizotinib is one of the molecularly-targeted agents targeted against anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC). Although its effects appear to be promising, crizotinib may cause adverse effects in patients with ALK-rearranged NSCLC. Hepatic laboratory abnormalities are frequently observed with crizotinib and treatment discontinuation is occasionally required. We herein report the case of a 51-year-old woman diagnosed with relapsed ALK-rearranged NSCLC, who received crizotinib as second-line systemic chemotherapy. After 17 days of crizotinib therapy, the patient developed grade >3 hepatotoxicity. Treatment discontinuation improved the laboratory abnormalities and fifth-line oral desensitization with crizotinib achieved successful response without hepatotoxicity. Therefore, oral desensitization with crizotinib may be a viable option following crizotinib-induced hepatitis. [ABSTRACT FROM AUTHOR]

We investigated the impact of defects formed at the SiO2/4H-SiC interface on the Schottky barrier height of metal/4H-SiC(0001) contacts. We found that an ultra-thin SiCxOy layer remains on the 4H-SiC surface after SiO2 sputtering at various powers and its removal by diluted hydro fluoride solution. Ni, Mo, or Al was deposited on 4H-SiC surface without and with a residual SiCxOy layer. It was found that metal/4H-SiC contacts without a residual SiCxOy layer exhibit ideal Schottky property, while Fermi-level pinning (FLP) is caused for metal/4H-SiC contacts with a residual SiCxOy layer, and the degree of FLP increases increasing sputtering power of SiO2. The pinning position was estimated to be ∼0.8 eV below the conduction band minimum of 4H-SiC, which does not correspond to the charge neutrality level of 4H-SiC. Finally, we proposed a physical model where a SiCxOy interlayer causes FLP, and the model was experimentally verified by intentionally forming a SiCxOy interlayer. [ABSTRACT FROM AUTHOR]