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Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma

Authors
 Jinsil Seong  ;  Sung Hee Kim  ;  Chang OK Suh 
Citation
 JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Vol.16(8) : 883-889, 2001 
Journal Title
 JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 
ISSN
 0815-9319 
Issue Date
2001
MeSH
Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use* ; Apoptosis/drug effects ; Apoptosis/radiation effects ; Carcinoma, Hepatocellular/drug therapy* ; Carcinoma, Hepatocellular/pathology ; Carcinoma, Hepatocellular/radiotherapy* ; Combined Modality Therapy ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/metabolism ; Dose-Response Relationship, Drug ; Liver Neoplasms/drug therapy* ; Liver Neoplasms/pathology ; Liver Neoplasms/radiotherapy* ; Male ; Mice ; Mice, Inbred C3H ; Radiation-Sensitizing Agents/pharmacology ; Radiation-Sensitizing Agents/therapeutic use* ; Random Allocation ; Up-Regulation
Keywords
apoptosis ; gemcitabine ; hepatocarcinoma ; p21WAF1/CIP1 ; radiation
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.
Full Text
http://onlinelibrary.wiley.com/doi/10.1046/j.1440-1746.2001.02533.x/abstract
DOI
10.1046/j.1440-1746.2001.02533.x
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Seong, Jin Sil(성진실) ORCID logo https://orcid.org/0000-0003-1794-5951
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/142294
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