Preclinical safety and efficacy of in situ REIC/Dkk-3 Gene therapy for prostate cancer

Keiichiro Kawauchi, Masami Watanabe, Haruki Kaku, Peng Huang, Kasumi Sasaki, Masakiyo Sakaguchi Ochiai, Nam ho Huh, Yasutomo Nasu, Hiromi Kumon

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)7-16
Number of pages10
JournalActa Medica Okayama
Volume66
Issue number1
Publication statusPublished - Feb 23 2012

Fingerprint

Gene therapy
Genetic Therapy
Tumors
Prostatic Neoplasms
Safety
Toxicity
Neoplasms
Neoplasm Genes
Therapeutic Uses
Tumor Suppressor Genes
Adenoviridae
Therapeutics
Spleen
Genes
Experiments
Cells
Body Weight
Tissue
Cell Line
Control Groups

Keywords

  • Dickkopf-3
  • Gene therapy
  • Preclinical study
  • Prostate cancer
  • Reic

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Kawauchi, K., Watanabe, M., Kaku, H., Huang, P., Sasaki, K., Ochiai, M. S., ... Kumon, H. (2012). Preclinical safety and efficacy of in situ REIC/Dkk-3 Gene therapy for prostate cancer. Acta Medica Okayama, 66(1), 7-16.

Preclinical safety and efficacy of in situ REIC/Dkk-3 Gene therapy for prostate cancer. / Kawauchi, Keiichiro; Watanabe, Masami; Kaku, Haruki; Huang, Peng; Sasaki, Kasumi; Ochiai, Masakiyo Sakaguchi; Huh, Nam ho; Nasu, Yasutomo; Kumon, Hiromi.

In: Acta Medica Okayama, Vol. 66, No. 1, 23.02.2012, p. 7-16.

Research output: Contribution to journalArticle

Kawauchi, K, Watanabe, M, Kaku, H, Huang, P, Sasaki, K, Ochiai, MS, Huh, NH, Nasu, Y & Kumon, H 2012, 'Preclinical safety and efficacy of in situ REIC/Dkk-3 Gene therapy for prostate cancer', Acta Medica Okayama, vol. 66, no. 1, pp. 7-16.
Kawauchi, Keiichiro ; Watanabe, Masami ; Kaku, Haruki ; Huang, Peng ; Sasaki, Kasumi ; Ochiai, Masakiyo Sakaguchi ; Huh, Nam ho ; Nasu, Yasutomo ; Kumon, Hiromi. / Preclinical safety and efficacy of in situ REIC/Dkk-3 Gene therapy for prostate cancer. In: Acta Medica Okayama. 2012 ; Vol. 66, No. 1. pp. 7-16.
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