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Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model

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Title: Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model
Authors: Murakami, Masahiro Browse this author
Zhao, Songji Browse this author →KAKEN DB
Zhao, Yan Browse this author
Yu, Wenwen Browse this author
Fatema, Chowdhury Nusrat Browse this author
Nishijima, Ken-Ichi Browse this author
Yamasaki, Masahiro Browse this author →KAKEN DB
Takiguchi, Mitsuyoshi Browse this author →KAKEN DB
Tamaki, Nagara Browse this author →KAKEN DB
Kuge, Yuji Browse this author →KAKEN DB
Keywords: fluorothymidine
positron emission tomography
tumor proliferation
anti-angiogenic therapy
Ki-67 labeling index
Issue Date: Sep-2013
Publisher: Spandidos Publ Ltd
Journal Title: Oncology Letters
Volume: 6
Issue: 3
Start Page: 667
End Page: 672
Publisher DOI: 10.3892/ol.2013.1459
Abstract: An early identification of the tumor response to sorafenib treatment is indispensable for selecting optimal personalized treatment strategies. However, at present, no reliable predictors are clinically available. F-18-fluorothymidine (F-18-FLT) positron emission tomography (PET) is used to assess tumor proliferation, since the FLT uptake level reflects thymidine kinase-1 (TK-1) activity. Thus, the present study determined whether FLT was able to evaluate the early tumor response to sorafenib treatment in a human renal cell carcinoma (RCC; A498) xenograft in comparison with the tumor proliferation marker, Ki-67. Mice bearing A498 tumors were assigned to the control and sorafenib-treated groups and the tumor volume was measured every day. [Methyl-3H(N)]-3'-fluoro-3'-deoxythymidine (H-3-FLT) was injected 2 h prior to the sacrifice of the mice on days three and seven following the treatment. H-3-FLT autoradiography (ARG) and Ki-67 immunohistochemistry (IHC) were performed using adjacent tumor sections. In the visual assessment, the intratumoral H-3-FLT uptake level diffusely increased following the treatment, while no significant changes were observed in Ki-67 IHC. The intratumoral H-3-FLT uptake levels significantly increased by 2.7- and 2.6-fold on days three and seven following the treatment, while the tumor volume and Ki-67 index did not significantly change. Thus, an increased FLT uptake level was demonstrated following the treatment, which may indicate the suppression of thymidylate synthase (TS) and the compensatory upregulation of TK-1 activity by sorafenib.
Type: article
URI: http://hdl.handle.net/2115/54744
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 趙 松吉

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