Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma

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Abstract

Background and Aims: Recent studies have shown that local radiotherapy can be an effective component of the treatment for hepatocellular carcinoma. To further improve therapeutic efficacy, use of drugs that can beneficially interact with radiation has been suggested. The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. Methods: C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-I, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by the use of a tumor growth delay assay and by an enhancement factor. The apoptotic level was assessed in tissue sections. The expression of regulating molecules was analyzed by using western blotting for p53, Bcl-2, Bax, Bcl-XL, Bcl-XS, and p21WAF1/CIP1. Results: Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with an enhancement factor of 1.6. The induction of apoptosis by a combination of gemcitabine and radiation was shown as only an additive level. In the analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine with radiation was the activation of p21WAF1/CIP1. Conclusion: Gemcitabine is the first to show an enhancement of radioresponse of murine hepatocarcinoma when combined with radiation. The key element of enhancement is thought to be p21WAF1/CIP1.

Original languageEnglish
Pages (from-to)883-889
Number of pages7
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume16
Issue number8
DOIs
Publication statusPublished - 2001 Jan 1

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gemcitabine
Radiation
Drug Therapy
Neoplasms
Pharmaceutical Preparations
Radiation Dosage
Inbred C3H Mouse
Radiation Effects
Therapeutic Uses
Paclitaxel
Doxorubicin
Cisplatin
Hepatocellular Carcinoma
Radiotherapy
Western Blotting
Apoptosis
Therapeutics
Growth

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

@article{257ead9943d447a783708b19e9ea242d,
title = "Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma",
abstract = "Background and Aims: Recent studies have shown that local radiotherapy can be an effective component of the treatment for hepatocellular carcinoma. To further improve therapeutic efficacy, use of drugs that can beneficially interact with radiation has been suggested. The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. Methods: C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-I, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by the use of a tumor growth delay assay and by an enhancement factor. The apoptotic level was assessed in tissue sections. The expression of regulating molecules was analyzed by using western blotting for p53, Bcl-2, Bax, Bcl-XL, Bcl-XS, and p21WAF1/CIP1. Results: Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with an enhancement factor of 1.6. The induction of apoptosis by a combination of gemcitabine and radiation was shown as only an additive level. In the analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine with radiation was the activation of p21WAF1/CIP1. Conclusion: Gemcitabine is the first to show an enhancement of radioresponse of murine hepatocarcinoma when combined with radiation. The key element of enhancement is thought to be p21WAF1/CIP1.",
author = "Jinsil Seong and Kim, {Sung Hee} and Suh, {Chang O.K.}",
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Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma. / Seong, Jinsil; Kim, Sung Hee; Suh, Chang O.K.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 16, No. 8, 01.01.2001, p. 883-889.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma

AU - Seong, Jinsil

AU - Kim, Sung Hee

AU - Suh, Chang O.K.

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N2 - Background and Aims: Recent studies have shown that local radiotherapy can be an effective component of the treatment for hepatocellular carcinoma. To further improve therapeutic efficacy, use of drugs that can beneficially interact with radiation has been suggested. The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. Methods: C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-I, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by the use of a tumor growth delay assay and by an enhancement factor. The apoptotic level was assessed in tissue sections. The expression of regulating molecules was analyzed by using western blotting for p53, Bcl-2, Bax, Bcl-XL, Bcl-XS, and p21WAF1/CIP1. Results: Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with an enhancement factor of 1.6. The induction of apoptosis by a combination of gemcitabine and radiation was shown as only an additive level. In the analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine with radiation was the activation of p21WAF1/CIP1. Conclusion: Gemcitabine is the first to show an enhancement of radioresponse of murine hepatocarcinoma when combined with radiation. The key element of enhancement is thought to be p21WAF1/CIP1.

AB - Background and Aims: Recent studies have shown that local radiotherapy can be an effective component of the treatment for hepatocellular carcinoma. To further improve therapeutic efficacy, use of drugs that can beneficially interact with radiation has been suggested. The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. Methods: C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-I, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by the use of a tumor growth delay assay and by an enhancement factor. The apoptotic level was assessed in tissue sections. The expression of regulating molecules was analyzed by using western blotting for p53, Bcl-2, Bax, Bcl-XL, Bcl-XS, and p21WAF1/CIP1. Results: Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with an enhancement factor of 1.6. The induction of apoptosis by a combination of gemcitabine and radiation was shown as only an additive level. In the analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine with radiation was the activation of p21WAF1/CIP1. Conclusion: Gemcitabine is the first to show an enhancement of radioresponse of murine hepatocarcinoma when combined with radiation. The key element of enhancement is thought to be p21WAF1/CIP1.

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