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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3543

Title: Topical and systemic immunoreaction triggered by intravesical chemotherapy in an N-butyl-N-(4-hydroxybutyl) nitorosamine induced bladder cancer mouse model.
Other Titles: N-ブチル-N-(4-ヒドロキシブチル)ニトロソアミン誘発膀胱癌マウスモデルを用いた膀胱内化学療法による局所及び全身の免疫応答
Authors: Hori, Shunta
Miyake, Makito
Tatsumi, Yoshihiro
Onishi, Sayuri
Morizawa, Yosuke
Nakai, Yasushi
Tanaka, Nobumichi
Fujimoto, Kiyohide
Issue Date: 13-Apr-2017
Publisher: Public Library of Science
Citation: PloS one Vol.12 No.4 Article No.e0175494 (2017 Apr)
Abstract: Intravesical bacillus Calmette-Guerin (BCG) treatment is the most common therapy to prevent progression and recurrence of non-muscle invasive bladder cancer (NMIBC). Although the immunoreaction elicited by BCG treatment is well documented, those induced by intravesical treatment with chemotherapeutic agents are much less known. We investigated the immunological profiles caused by mitomycin C, gemcitabine, adriamycin and docetaxel in the N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced orthotopic bladder cancer mouse model. Ninety mice bearing orthotopic bladder cancer induced by BBN were randomly divided into six groups and treated with chemotherapeutic agents once a week for four weeks. After last treatment, bladder and serum samples were analyzed for cell surface and immunological markers (CD4, CD8, CD56, CD204, Foxp3, and PD-L1) using immunohistochemistry staining. Serum and urine cytokine levels were evaluated by ELISA. All chemotherapeutic agents presented anti-tumor properties similar to those of BCG. These included changes in immune cells that resulted in fewer M2 macrophages and regulatory T cells around tumors. This result was compatible with those in human samples. Intravesical chemotherapy also induced systemic changes in cytokines, especially urinary interleukin (IL)-17A and granulocyte colony stimulating factor (G-CSF), as well as in the distribution of blood neutrophils, lymphocytes, and monocytes. Our findings suggest that intravesical treatment with mitomycin C and adriamycin suppresses protumoral immunity while enhancing anti-tumor immunity, possibly through the action of specific cytokines. A better understanding of the immunoreaction induced by chemotherapeutic agents can lead to improved outcomes and fewer side effects in intravesical chemotherapy against NMIBC.
Description: 博士(医学)・甲第695号・平成31年3月15日
Copyright: © 2017 Hori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
URI: http://hdl.handle.net/10564/3543
ISSN: 19326203
DOI: http://dx.doi.org/10.1371/journal.pone.0175494
Academic Degrees and number: 24601A695
Degree-granting date: 2019-03-15
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2018年度

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