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JaLCDOI 10.18926/AMO/48076
FullText URL 66_1_7.pdf
Author Kawauchi, Keiichiro| Watanabe, Masami| Kaku, Haruki| Huang, Peng| Sasaki, Kasumi| Sakaguchi, Masakiyo| Ochiai, Kazuhiko| Huh, Nam-ho| Nasu, Yasutomo| Kumon, Hiromi|
Abstract The preclinical safety and therapeutic efficacy of adenoviral vectors that express the REIC/Dkk-3 tumor suppressor gene (Ad-REIC) was examined for use in prostate cancer gene therapy. The Ad-human (h) and mouse (m) REIC were previously demonstrated to induce strong anti-cancer effects in vitro and in vivo, and we herein report the results of two in vivo studies. First, intra-tumor Ad-hREIC administration was examined for toxicity and therapeutic effects in a subcutaneous tumor model using the PC3 prostate cancer cell line. Second, intra-prostatic Ad-mREIC administration was tested for toxicity in normal mice. The whole-body and spleen weights, hematological and serum chemistry parameters, and histological evaluation of tissues from throughout the body were analyzed. Both experiments indicated that there was no significant difference in the examined parameters between the Ad-REIC-treated group and the control (PBS- or Ad-LacZ-treated) group. In the in vitro analysis using PC3 cells, a significant apoptotic effect was observed after Ad-hREIC treatment. Confirming this observation, the robust anti-tumor efficacy of Ad-hREIC was demonstrated in the in vivo subcutaneous prostate cancer model. Based on the results of these preclinical experiments, we consider the adenovirus-mediated REIC/Dkk-3 in situ gene therapy to be safe and useful for the clinical treatment of prostate cancer.
Keywords REIC Dickkopf-3 gene therapy prostate cancer preclinical study
Amo Type Original Article
Publication Title Acta Medica Okayama
Published Date 2012-02
Volume volume66
Issue issue1
Publisher Okayama University Medical School
Start Page 7
End Page 16
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2012 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 22358134
Web of Science KeyUT 000300800700002
JaLCDOI 10.18926/AMO/48075
FullText URL 66_1_1.pdf
Author Udono, Heiichiro|
Abstract Dendritic cells (DCs) take up soluble- or cell-associated antigens and digest them, delivering fragments to the MHC class I pathway to display antigenic peptides to CD8+ T cells, a process known as cross-presentation. The pathway requires that, in order to be degraded by proteosomes, the extracellular antigens must have access to the cytosol across the endosomal membranes. Although the cross-presentation phenomena was first identified in the 1970s, the molecular mechanism responsible for the translocation is still not fully understood. In this context, we have recently found that cytosolic heat shock protein (HSP)90 translocates internalized antigen to the cytosol in DCs. Our results revealed the important role that cytosolic HSP90 plays in cross-presentation by pulling out endosomal antigen to the cytosol.
Keywords heat shock protein 90 dendritic cells cross-presentation proteasome cytotoxic T cell immunity
Amo Type Review
Publication Title Acta Medica Okayama
Published Date 2012-02
Volume volume66
Issue issue1
Publisher Okayama University Medical School
Start Page 1
End Page 6
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2012 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 22358133
Web of Science KeyUT 000300800700001
Author 岡山医学会|
Published Date 1918-10-31
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue345
Content Type Others
Author 岡山医学会|
Published Date 1918-10-31
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue345
Content Type Others
Author 横川 定| 末盛 進|
Published Date 1918-10-31
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue345
Content Type Journal Article
Author 吉田 千束|
Published Date 1918-10-31
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue345
Content Type Journal Article
Author 林 昇| 富岡 敏哉|
Published Date 1918-10-31
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue345
Content Type Journal Article
Author 渡邊 善朝|
Published Date 1918-10-31
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue345
Content Type Journal Article
Author 上坂 熊勝| 關 正次|
Published Date 1918-10-31
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue345
Content Type Journal Article
Author 岡山医学会|
Published Date 1918-09-30
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue344
Content Type Others
Author 岡山医学会|
Published Date 1918-09-30
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue344
Content Type Others
Author 田邊 郁郎|
Published Date 1918-09-30
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue344
Content Type Journal Article
Author 横川 定| 末盛 進|
Published Date 1918-09-30
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue344
Content Type Journal Article
Author 天川 保|
Published Date 1918-09-30
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue344
Content Type Journal Article
Author 野上 尚志|
Published Date 1918-09-30
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue344
Content Type Journal Article
Author 岡山医学会|
Published Date 1918-08-31
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue343
Content Type Others
Author 高橋 金一郎|
Published Date 1918-08-31
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue343
Content Type Article
Author 横川 定|
Published Date 1918-08-31
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue343
Content Type Journal Article
Author 中田 理吉|
Published Date 1918-08-31
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue343
Content Type Journal Article
Author 吉田 千束|
Published Date 1918-08-31
Publication Title 岡山医学会雑誌
Volume volume30
Issue issue343
Content Type Journal Article