城西大学機関リポジトリJURAPEGPH20, a PEGylated human hyaluronidase, induces radiosensitization by reoxygenation in pancreatic cancer xenografts. A molecular imaging study

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PEGPH20, a PEGylated human hyaluronidase, induces radiosensitization by reoxygenation in pancreatic cancer xenografts. A molecular imaging study

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ID	JOS-j.neo.2022.100793
著者：名前	関, 智宏/才田, 優/Kishimoto, Shun/Lee, Jisook/音羽, 泰則/Yamamoto, Kazutoshi/Chandramouli, Gadisetti VR/Devasahayam, Nallathamby/Mitchell, James B./Krishna, Murali C./Brender, Jeffery R.
著者：別形式	Seki, Tomohiro / Saida, Yu / Kishimoto, Shun / Lee, Jisook / Otowa a, Yasunori / Yamamoto, Kazutoshi / Chandramouli, Gadisetti VR / Devasahayam, Nallathamby / Mitchell, James B. / Krishna, Murali C. / Brender, Jeffery R.
著者：カナ	セキ, トモヒロ/サイダ, ユウ/キシモト, シュン/Lee, Jisook/オトワ, ヤスノリ/ヤマモト, カズトシ/Chandramouli, Gadisetti VR/Devasahayam, Nallathamby/Mitchell, James B./Krishna, Murali C./Brender, Jeffery R.
著者：所属	城西大学薬学部 / 新潟大学医歯学総合病院呼吸器・感染症内科 / National Cancer Institute, Center for Cancer Research, Radiation Biology Branch / Halozyme Therapeutics / National Cancer Institute, Center for Cancer Research, Radiation Biology Branch / National Cancer Institute, Center for Cancer Research, Radiation Biology Branch / National Cancer Institute, Center for Cancer Research, Radiation Biology Branch / National Cancer Institute, Center for Cancer Research, Radiation Biology Branch / National Cancer Institute, Center for Cancer Research, Radiation Biology Branch / National Cancer Institute, Center for Cancer Research, Radiation Biology Branch / National Cancer Institute, Center for Cancer Research, Radiation Biology Branch
著者：所属(別形式）	Josai University, Faculty of Pharmaceutical Sciences / Niigata University Medical and Dental Hospital, Department of Respiratory Medicine and Infectious Diseases / National Cancer Institute, Center for Cancer Research, Radiation Biology Branch / Halozyme Therapeutics / National Cancer Institute, Center for Cancer Research, Radiation Biology Branch / National Cancer Institute, Center for Cancer Research, Radiation Biology Branch / National Cancer Institute, Center for Cancer Research, Radiation Biology Branch / National Cancer Institute, Center for Cancer Research, Radiation Biology Branch / National Cancer Institute, Center for Cancer Research, Radiation Biology Branch / National Cancer Institute, Center for Cancer Research, Radiation Biology Branch / National Cancer Institute, Center for Cancer Research, Radiation Biology Branch
著者版フラグ	publisher
出版地	Cambridge
出版者	Elsevier
冊子ISSN	15228002
電子ISSN	14765586
掲載誌名	Neoplasia
巻	30
号	C
刊行年月	2022-08
開始ページ	1
終了ページ	13
コンテンツ作成日	2022-02-09
コンテンツ修正日	2022-03-29
コンテンツ登録日	2023-02-20
識別番号：DOI	info:doi/10.1016/j.neo.2022.100793
識別番号：DOI（リンク）	https://doi.org/10.1016/j.neo.2022.100793
PubMed番号	35523073
抄録	Purpose: PEGylated human hyaluronidase (PEGPH20) enzymatically depletes hyaluronan, an important component of the extracellular matrix, increasing the delivery of therapeutic molecules. Combinations of chemotherapy and PEGPH20, however, have been unsuccessful in Phase III clinical trials. We hypothesize that by increasing tumor oxygenation by improving vascular patency and perfusion, PEGPH20 will also act as a radiosensitization agent.Experimental design: The effect of PEGPH20 on radiation treatment was analyzed with respect to tumor growth, survival time, p02, local blood volume, and the perfusion/permeability of blood vessels in a human pancreatic adenocarcinoma BxPC3 mouse model overexpressing hyaluronan synthase 3 (HAS3).Results: Mice overexpressing HAS3 developed fast growing, radiation resistant tumors that became rapidly more hypoxic as time progressed. Treatment with PEGPH20 increased survival times when used in combination with radiation therapy, significantly more than either radiation therapy or PEGPH20 alone. In mice that overexpressed HAS3, EPR imaging showed an increase in local pO2 that could be linked to increases in perfusion/permeability and local blood volume immediately after PEGPH20 treatment. Hyperpolarized [1-13C] pyruvate suggested PEGPH20 caused a metabolic shift towards decreased glycolytic flux. These effects were confined to the mice overexpressing HAS3 - no effect of PEGPH20 on survival, radiation treatment, or pO2 was seen in wild type BxPC3 tumors.Conclusions: PEGPH20 may be useful for radiosensitization of pancreatic cancer but only in the subset of tumors with substantial hyaluronan accumulation. The response of the treatment may potentially be monitored by non-invasive imaging of the hemodynamic and metabolic changes in the tumor microenvironment.
キーワード	PEGPH20/Hypoxia/Tumor Microenvironment/Radiation Resistance/Pancreatic Cancer/Preclinical
注記	Article 100793
言語	eng
資源タイプ	text
ジャンル	01学術雑誌論文 / Journal Article
フォーマット	application/pdf
権利	Copyright © 2022 The Authors.
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このアイテムを表示する：URI	https://libir.josai.ac.jp/il/meta_pub/G0000284repository_JOS-j.neo.2022.100793

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