von Willebrand Factor-Rich Platelet Thrombi in the Liver Cause Sinusoidal Obstruction Syndrome following Oxaliplatin-Based Chemotherapy.

• Material Type: 博士論文
• Title: von Willebrand Factor-Rich Platelet Thrombi in the Liver Cause Sinusoidal Obstruction Syndrome following Oxaliplatin-Based Chemotherapy.
• Author/Editor: Nishigori, Naoto; Matsumoto, Masanori; Koyama, Fumikazu; Hayakawa, Masaki; Hatakeyama, Kinta; Ko, Saiho; Fujimura, Yoshihiro; Nakajima, Yoshiyuki
• Author Heading: Nishigori, Naoto; Matsumoto, Masanori; Koyama, Fumikazu; Hayakawa, Masaki; Hatakeyama, Kinta; Ko, Saiho; Fujimura, Yoshihiro; Nakajima, Yoshiyuki
• Publication, Distribution, etc.: Public Library of Science
• Publication Date: 2015-11-18
• Publication Date (W3CDTF): 2015-11-18
• Alternative Title: Oxaliplatinによる肝類洞障害は肝臓内にvon Willebrand因子が血小板血栓を形成することにより発症する
• Periodical title: PloS one
• No. or year of volume/issue: 10 11
• Volume: 10
• Issue: 11
• Pages: Article No.e0143136-
• ISSN (Periodical Title): ISSN : 1932-6203
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2016-03-15
• Dissertation Number: 乙第1373号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Target Audience: 一般
• Note (General): type:Thesis; Oxaliplatin-based chemotherapy is widely used to treat advanced colorectal cancer (CRC). Sinusoidal obstruction syndrome (SOS) due to oxaliplatin is a serious type of chemotherapy-associated liver injury (CALI) in CRC patients. SOS is thought to be caused by the sinusoidal endothelial cell damage, which results in the release of unusually-large von Willebrand factor multimers (UL-VWFMs) from endothelial cells. To investigate the pathophysiology of CALI after oxaliplatin-based chemotherapy, we analyzed plasma concentration of von Willebrand factor (VWF) and the distribution of VWFMs in CRC patients. Twenty-three patients with advanced CRC who received oxaliplatin-based chemotherapy with (n = 6) and without (n = 17) bevacizumab were analyzed. CALI (n = 6) and splenomegaly (n = 9) were found only in patients who did not treated with bevacizumab. Plasma VWF antigen (VWF:Ag) and serum aspartate aminotransferase (AST) levels increased after chemotherapy only in patients without bevacizumab. VWFM analysis in patients who did not receive bevacizumab showed the presence of UL-VWFMs and absence of high molecular weight VWFMs during chemotherapy, especially in those with CALI. In addition, plasma VWF:Ag and AST levels increased after chemotherapy in patients with splenomegaly (n = 9), but not in patients without splenomegaly (n = 14). Histological findings in the liver tissue of patients who did not receive bevacizumab included sinusoidal dilatation and microthrombi in the sinusoids. Many microthrombi were positive for both anti-IIb/IIIa and anti-VWF antibodies. Plasma UL-VWFM levels might be increased by damage to endothelial cells as a result of oxaliplatin-based chemotherapy. Bevacizumab could prevent CALI and splenomegaly through inhibition of VWF-rich platelet thrombus formation.; 博士（医学）・乙第1373号・平成28年3月15日; Copyright: © 2015 Nishigori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.; identifier:PloS one Vol.10 No.11 Article No.e0143136 (2015.11); identifier:19326203; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3196; identifier:PloS one, 10(11): Article No.e0143136
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1371/journal.pone.0143136
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3196/1/01_%e4%b9%991373%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3196/5/03_%e4%b9%991373%e6%9c%ac%e6%96%87.pdf fulltext