Publications by authors named "Norikazu Une"

3 Publications

  • Page 1 of 1

The anti-angiogenic agent lenvatinib induces tumor vessel normalization and enhances radiosensitivity in hepatocellular tumors.

Med Oncol 2021 Apr 21;38(6):60. Epub 2021 Apr 21.

Department of Medical Physics, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.

The evaluation of angiogenesis inhibitors requires the analysis of the precise structure and function of tumor vessels. The anti-angiogenic agents lenvatinib and sorafenib are multi-target tyrosine kinase inhibitors that have been approved for the treatment of hepatocellular carcinoma (HCC). However, the different effects on tumor vasculature between lenvatinib and sorafenib are not well understood. In this study, we analyzed the effects of both drugs on vascular structure and function, including vascular normalization, and investigated whether the normalization had a positive effect on a combination therapy with the drugs and radiation using micro X-ray computed tomography with gold nanoparticles as a contrast agent, as well as immunohistochemical analysis and interstitial fluid pressure (IFP) measurement. In mice subcutaneously transplanted with mouse HCC cells, treatment with lenvatinib or sorafenib for 14 days inhibited tumor growth and reduced the tumor vessel volume density. However, analysis of integrated data on vessel density, rates of pericyte-covering and perfused vessels, tumor hypoxia, and IFP measured 4 days after drug treatment showed that treatment with 3 mg/kg of lenvatinib significantly reduced the microvessel density and normalized tumor vessels compared to treatment with 50 mg/kg of sorafenib. These results showed that lenvatinib induced vascular normalization and improved the intratumoral microenvironment in HCC tumors earlier and more effectively than sorafenib. Moreover, such changes increased the radiosensitivity of tumors and enhanced the effect of lenvatinib and radiation combination therapy, suggesting that this combination therapy is a powerful potential application against HCC.
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http://dx.doi.org/10.1007/s12032-021-01503-zDOI Listing
April 2021

Development of X-ray contrast agents using single nanometer-sized gold nanoparticles and lactoferrin complex and their application in vascular imaging.

Colloids Surf B Biointerfaces 2021 Apr 1;203:111732. Epub 2021 Apr 1.

Department of Medical Physics, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan; International Center for Synchrotron Radiation InnovationSmart (SRIS), Tohoku University, 2-1-1, Katahira, Aoba-ku, Sendai 980-8577, Japan. Electronic address:

The technology to accurately image the morphology of tumor vessels with X-ray contrast agents is important to clarify mechanisms underlying tumor progression and evaluate the efficacy of chemotherapy. However, in clinical practice, iodine-based contrast agents present problems such as short blood retention owing to a high clearance ability and insufficient X-ray absorption capacity when compared with other high atomic number elements. To resolve these issues, gold nanoparticles (AuNPs), with a high atomic number, have attracted a great deal of attention as contrast agents for angiography, and have been employed in small animal models. Herein, we developed novel contrast agents using AuNPs and captured changes in tumor vessel morphology with time using X-ray computed tomography (CT). First, glutathione-supported single nanometer-sized AuNPs (sAu/GSH) (diameter, 2.2 nm) were fabricated using tetrakis(hydroxymethyl)phosphonium chloride as a reducing agent. The sAu/GSH particles were intravenously injected into mice, remained in vessels for a few minutes, and were then excreted by the kidneys after 24 h, similar to the commercial contrast agent iopamidol. Next, the Au/GSH and lactoferrin (sAu/GSH-LF) (long axis size, 17.3 nm) complex was produced by adding lactoferrin to the sAu/GSH solution under the influence of a condensing agent. On intravenously administering sAu/GSH-LF to mice, the blood retention time was 1-3 h, which was considerably longer than that observed with iopamidol and sAu/GSH. Moreover, we succeeded in imaging morphological changes in identical tumor vessels for several days using X-ray CT with sAu/GSH-LF.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111732DOI Listing
April 2021

[A Case of Curatively Resected Rectal Cancer with Preservation of Urinary Function after Chemotherapy].

Gan To Kagaku Ryoho 2019 Apr;46(4):820-822

Dept. of Surgery, Tohoku University Graduate School of Medicine.

A55 -year-old man was diagnosed with rectal cancer invading the urinary bladder and swollen para-aortic lymph nodes. Since distant metastasis was indicated and total pelvic exenteration was required, 6 courses of chemotherapy with mFOLFOX6 plus panitumumab were performed. After the chemotherapy, the rectal cancer and para-aortic lymph nodes significantly decreased in size, and novel distant metastasis was not observed in CT scans. Therefore, the tumor was considered resectable, and operation was performed. Intraoperative frozen section analysis showed that the para-aortic lymph nodes and surgical margin of the urinary bladder were negative. Thus, low anterior resection of the rectum and partial resection of the urinary bladder were performed. R0 resection was pathologically achieved, and adjuvant chemotherapy with S-1 was administered for 6 months. The patient is alive without recurrence for 10 months. Upfront chemotherapy can be a strategy for advanced rectal cancer with urinary bladder invasion to avoid total pelvic exenteration.
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April 2019