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Title: Treatment Combining X-Irradiation and a Ribonucleoside Anticancer Drug, TAS106, Effectively Suppresses the Growth of Tumor Cells Transplanted in Mice

Abstract

Purpose: To examine the in vivo antitumor efficacy of X-irradiation combined with administration of a ribonucleoside anticancer drug, 1-(3-C-ethynyl-{beta}-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd), to tumor cell-transplanted mice. Methods and Materials: Colon26 murine rectum adenocarcinoma cells and MKN45 human gastric adenocarcinoma cells were inoculated into the footpad in BALB/c mice and severe combined immunodeficient mice, respectively. They were treated with a relatively low dose of X-irradiation (2 Gy) and low amounts of TAS106 (0.1 mg/kg and 0.5 mg/kg). The tumor growth was monitored by measuring the tumor volume from Day 5 to Day 16 for Colon26 and from Day 7 to Day 20 for MKN45. Histologic analyses for proliferative and apoptotic cells in the tumors were performed using Ki-67 immunohistochemical and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. The expression of survivin, a key molecule related to tumor survival, was assessed by quantitative polymerase chain reaction and immunohistochemical analysis. Results: When X-irradiation and TAS106 treatment were combined, significant inhibition of tumor growth was observed in both types of tumors compared with mice treated with X-irradiation or TAS106 alone. Marked inhibition of tumor growth was observed in half of the mice that received the combined treatment three times at 2-day intervals. Parallel to thesemore » phenomena, the suppression of survivin expression and appearance of Ki-67-negative and apoptotic cells were observed. Conclusions: X-irradiation and TAS106 effectively suppress tumor growth in mice. The inhibition of survivin expression by TAS106 is thought to mainly contribute to the suppression of the tumor growth.« less

Authors:
 [1];  [1];  [1];  [1];  [2];  [3];  [4];  [5]
  1. Laboratory of Radiation Biology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo (Japan)
  2. Department of Veterinary Anatomy, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka (Japan)
  3. Laboratory of Anatomy, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo (Japan)
  4. Laboratory of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo (Japan)
  5. Laboratory of Radiation Biology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo (Japan). E-mail: kuwabara@vetmed.hokudai.ac.jp
Publication Date:
OSTI Identifier:
20951636
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 68; Journal Issue: 1; Other Information: DOI: 10.1016/j.ijrobp.2006.12.061; PII: S0360-3016(07)00093-4; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANTINEOPLASTIC DRUGS; BIOLOGICAL WARFARE AGENTS; CARCINOMAS; CYTOSINE; GROWTH; IN VIVO; INHIBITION; IRRADIATION; LABELLING; MICE; POLYMERASE CHAIN REACTION; POTASSIUM IODIDES; RADIATION DOSES; RECTUM; TUMOR CELLS

Citation Formats

Yasui, Hironobu, Inanami, Osamu, Asanuma, Taketoshi, Iizuka, Daisuke, Nakajima, Takayuki, Kon, Yasuhiro, Matsuda, Akira, and Kuwabara, Mikinori. Treatment Combining X-Irradiation and a Ribonucleoside Anticancer Drug, TAS106, Effectively Suppresses the Growth of Tumor Cells Transplanted in Mice. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.12.061.
Yasui, Hironobu, Inanami, Osamu, Asanuma, Taketoshi, Iizuka, Daisuke, Nakajima, Takayuki, Kon, Yasuhiro, Matsuda, Akira, & Kuwabara, Mikinori. Treatment Combining X-Irradiation and a Ribonucleoside Anticancer Drug, TAS106, Effectively Suppresses the Growth of Tumor Cells Transplanted in Mice. United States. doi:10.1016/j.ijrobp.2006.12.061.
Yasui, Hironobu, Inanami, Osamu, Asanuma, Taketoshi, Iizuka, Daisuke, Nakajima, Takayuki, Kon, Yasuhiro, Matsuda, Akira, and Kuwabara, Mikinori. Tue . "Treatment Combining X-Irradiation and a Ribonucleoside Anticancer Drug, TAS106, Effectively Suppresses the Growth of Tumor Cells Transplanted in Mice". United States. doi:10.1016/j.ijrobp.2006.12.061.
@article{osti_20951636,
title = {Treatment Combining X-Irradiation and a Ribonucleoside Anticancer Drug, TAS106, Effectively Suppresses the Growth of Tumor Cells Transplanted in Mice},
author = {Yasui, Hironobu and Inanami, Osamu and Asanuma, Taketoshi and Iizuka, Daisuke and Nakajima, Takayuki and Kon, Yasuhiro and Matsuda, Akira and Kuwabara, Mikinori},
abstractNote = {Purpose: To examine the in vivo antitumor efficacy of X-irradiation combined with administration of a ribonucleoside anticancer drug, 1-(3-C-ethynyl-{beta}-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd), to tumor cell-transplanted mice. Methods and Materials: Colon26 murine rectum adenocarcinoma cells and MKN45 human gastric adenocarcinoma cells were inoculated into the footpad in BALB/c mice and severe combined immunodeficient mice, respectively. They were treated with a relatively low dose of X-irradiation (2 Gy) and low amounts of TAS106 (0.1 mg/kg and 0.5 mg/kg). The tumor growth was monitored by measuring the tumor volume from Day 5 to Day 16 for Colon26 and from Day 7 to Day 20 for MKN45. Histologic analyses for proliferative and apoptotic cells in the tumors were performed using Ki-67 immunohistochemical and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. The expression of survivin, a key molecule related to tumor survival, was assessed by quantitative polymerase chain reaction and immunohistochemical analysis. Results: When X-irradiation and TAS106 treatment were combined, significant inhibition of tumor growth was observed in both types of tumors compared with mice treated with X-irradiation or TAS106 alone. Marked inhibition of tumor growth was observed in half of the mice that received the combined treatment three times at 2-day intervals. Parallel to these phenomena, the suppression of survivin expression and appearance of Ki-67-negative and apoptotic cells were observed. Conclusions: X-irradiation and TAS106 effectively suppress tumor growth in mice. The inhibition of survivin expression by TAS106 is thought to mainly contribute to the suppression of the tumor growth.},
doi = {10.1016/j.ijrobp.2006.12.061},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 68,
place = {United States},
year = {Tue May 01 00:00:00 EDT 2007},
month = {Tue May 01 00:00:00 EDT 2007}
}