skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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}
}
  • Gastrodia elata Blume (G. elata) is a famous restorative food in East Asia. It can be used as an auxiliary reagent in hepatocellular carcinoma (HCC) treatment. Previous studies unveiled that G. elata exhibited immunomodulatory activities. To explore the active ingredients contributing to its immunomodulatory activities, gastrodin, vanillin, and parishin B were purified from G. elata and their anti-HCC effects were assessed in vivo. Among these compounds, only gastrodin was capable of repressing transplanted H22 ascitic hepatic tumor cell growth in vivo with low toxicity. Further investigations were designed to explore the effects of gastrodin on the immune system of tumor-bearingmore » mice and potential molecular mechanisms underlying these effects. Our data showed that gastrodin ameliorated tumor cell transplantation-induced activation of endogenous pro-apoptotic pathway in CD4 + T cells and abnormalities in serum cytokine profiles in host animals. These events enhanced cytotoxic activities of natural killer and CD8 + T cells against H22 hepatic cancer cells. Gastrodin administration specifically upregulated mRNA levels of several nuclear factor κB (NF-κB) responsive genes in CD4 + T cells but not in CD8 + T cells. Chromatin immunoprecipitation assay showed that gastrodin increased the association of NF-κB p65 subunit to the promoter regions of IL-2 and Bcl-2 encoding genes in CD4 + T cells. Our investigations demonstrated that gastrodin is the main active ingredient contributing to the anticancer immunomodulatory properties of G. elata. Promoting NF-κB-mediated gene transcription in CD4 + T cells is implicated in its immunomodulatory activity. - Highlights: • Gastrodin stimulates anticancer immune response. • Gastrodin represses tumor transplantation-induced CD4 + T cell apoptosis. • Gastrodin activates NF-κB activity in CD4 + T cells.« less
  • A human malignant melanoma transplanted into nude mice was exposed to single-dose x irradiation. Experimental growth data described mathematically according to a transformed Gompertz function were used to determine the effect of irradiation on growth delay, growth rate, and tumor shrinkage. The radiation-induced changes in the histology of the tumors were also described. The results showed that irradiation induced a dose-dependent growth delay; this parameter was therefore found suitable for the assessment of relative therapeutic effect. The treatment also induced a dose-dependent reduction in growth rate during regrowth. As a result of this effect on growth rate, extrapolation of tumormore » shrinkage to the time of treatment became directly misleading as a measure of the effect of the treatment. From this it can be deduced that in therapeutic studies where treatment induces nonparallel posttherapeutic growth curves, growth delay for various tumors and therapies cannot be compared directly. The transformed Gompertz function proved to be extremely well suited for evaluating these conditions.« less
  • Purpose: Control of cancer metastasis is one of the most important issues in cancer treatment. We previously demonstrated that carbon particle irradiation suppresses the metastatic potential of cancer cells, and many studies have reported that photon irradiation promotes it. The purpose of this study was to investigate the effect of carbon beam on non-small-cell lung cancer (NSCLC) cell aggressiveness and gene expression. Methods and Materials: A549 (lung adenocarcinoma) and EBC-1 (lung squamous cell carcinoma) cells were treated with 290 MeV/nucleon carbon ion beam at the Heavy Ion Medical Accelerator in Chiba or with 4-MV X-ray at Osaka University. We testedmore » proliferative, migratory, and invasive activities by cell proliferation assay, Boyden chamber assay, and Matrigel chemoinvasion assay, respectively. cDNA microarray and reverse transcription polymerase chain reaction were also performed to assess mRNA expression alteration. Results: X-irradiation increased cell proliferation of A549 cells at 0.5 Gy, whereas high-dose X-ray reduced migration and invasion of A549 cells. By contrast, carbon beam irradiation did not enhance proliferation, and it reduced the migration and invasion capabilities of both A549 and EBC-1 cells more effectively than did X-irradiation. Carbon beam irradiation induced alteration of various gene expression profiles differently from X-ray irradiation. mRNA expression of ANLN, a homologue of anillin, was suppressed to 60% levels of basal expression in carbon beam-irradiated A549 cells after 12 h. Conclusion: Carbon beam effectively suppresses the metastatic potential of A549 and EBC-1 cells. Carbon beam also has different effects on gene expressions, and downregulation of ANLN was induced only by carbon beam irradiation.« less
  • It was demonstrated, in experiments on LL cell cultures obtained from NKLy ascites lymphosarcoma of mice, that the curve of cell survival as function of dosage of methylnitrosourea is deprived of an arm at the logarithmic stage of growth, unlike cells in the stationary phase; in these populations, there are insignificant differences in values of D/sub 0/ doses. When added before and after irradiation, methyl nitrosourea increases radiation destruction of cells, and it is more effective when added before irradiation. The authors discuss molecular and cellular mechanisms of enhancement of effectiveness of radiation by methyl nitrosourea.