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Long-lasting responses after discontinuation of nivolumab treatment for reasons other than tumor progression in patients with previously treated,advanced non-small cell lung cancer

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Cancer Communications 2019年第1期39卷 665-669页

作者： Hideharu Kimura Tomoyuki Araya Taro Yoneda Hiroki Shirasaki Koji Kurokawa tamami sakai Hayato Koba Yuichi Tambo Shingo Nishikawa Takashi Sone Kazuo Kasahara Respiratory Medicine Kanazawa University HospitalTakara-machi 13-1KanazawaIshikawa 920-8641Japan Respiratory Medicine National Hospital Organization Kanazawa Medical CenterKanazawaIshikawa 920-8650Japan Respiratory Medicine Komatsu Municipal HospitalKomatsuIshikawa 923-8560Japan Respiratory Medicine Fukui-ken Saiseikai HospitalFukuiFukui 918-8503Japan Respiratory Medicine Ishikawa Prefectural Central HospitalKanazawaIshikawa 920-8530Japan Internal Medicine Keiju Medical CenterNanaoIshikawa 926-8605Japan Regional Respiratory Symptomatology Kanazawa University Graduate School of Medical ScienceKanazawaIshikawa 920-8641Japan

Dear Editor,Nivolumab,an inhibitor of programmed cell death 1(PD-1),is an immune checkpoint inhibitor(ICI)that enhances T cell functions by preventing negative regulation of cancer immunity,and it has shown clinically significant efficacy and tolerability in various types of *** on the results of randomized phase III trials comparing nivolumab with docetaxel[1,2],nivolumab is now used in clinical practice for patients with previously treated advanced non-small cell lung cancer(NSCLC).Fur-thermore,the most recent Japan Lung Cancer Society guidelines include nivolumab monotherapy in the sys-temic treatment strategy for previously treated,locally advanced or metastatic NSCLC[3].However,ICIs induce characteristic immune-related adverse events(irAEs),which are not seen with conventional cytotoxic agents or molecular targeted *** can occur in any organ system,most typically the skin,lung,and gastrointesti-nal,hepatic,and endocrine systems.

关键词： nivolumab patients lung

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Neuroprotective Effect of a Prostacyclin Agonist (ONO-1301) with Thromboxane Synthase Inhibitory Activity in Rats Subjected to Cerebral Ischemia

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Pharmacology & Pharmacy 2011年第4期2卷 306-314页

作者： Mai Hazekawa Yoshiki sakai Miyako Yoshida tamami Haraguchi Takahiro Uchida 不详

ONO-1301 has been developed as a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. In the present study, we investigated the cerebroprotective effect of ONO-1301 on post-ischemic injury induced by cerebral ischemia in rats. ONO-1301 (1 and 10 mg/kg) was administrated orally at reperfusion and then twice a day for 42 days. The cell damage induced by cerebral ischemia in the hippocampal CA1 was evaluated using both Nissl staining and proliferating cell nuclear antigen (PCNA) staining on the 42 days after cerebral ischemia. Activated astrocytes were evaluated using immunofluorescence staining with GFAP on the 42 days after cerebral ischemia. Spatial learning was assessed using a Morris water maze (MWM) task on the 56 days (i.e. after a 14 days washout period). ONO-1301- treated rats (1 and 10 mg/kg) significantly improved cell death in the hippocampal CA1, the number of PCNA-positive cells and astrocyte activation. The spatial learning of ONO-1301-treated rats compared with vehicle- treated rats in the MWM task. These results suggest that repeated treatment with oral ONO-1301 could prevent or limit post-ischemic brain damage. In particular, treatment with ONO-1301 within 7 days after ischemia is most effective to improve ischemic damage.

关键词： ONO-1301 Prostacyclin Agonist Neuroprotection Cerebral Ischemia Astrocytes

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