Document Detail


Anti-tumor effects of 25-hydroxycholesterol and low-dose recombinant tumor necrosis factor-alpha on rat liver tumorigenesis: modulated differentiation therapy for hepatocellular carcinoma.
MedLine Citation:
PMID:  10762641     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previously, we have demonstrated that treatment of rat AH136B ascites hepatoma cells with 25-hydroxycholesterol (25-OH) induces apoptosis. In this study, to elucidate whether modulated differentiation therapy may be useful in treating patients with hepatoma, we assayed the effects of 25-OH and/or tumor necrosis factor-alpha (TNF) on rat AH136B ascites hepatoma cells in vivo. Here we show that a high concentration of TNF (250 U/ml) mediated a stronger cytocidal effect than a low concentration of TNF (25 U/ml) in vitro. Flow cytometric DNA analysis also showed that treatment of cells with the high concentration of TNF (250 U/ml) increased the percentage of AH136B cells in the G0/G1 phase, while 25 U/ml of TNF did not cause any marked change in cell kinetics. In in vivo experiments, 25-OH (80 microg/rat) and TNF (500 U/rat) were administered after transplanting AH136B cells into Donryu rats intraperitoneally. We found that tumor development was completely inhibited by this treatment in 3 of 9 rats, and their 40-day survival rate was 44%; in contrast, rats administered 25-OH (80 microg/rat) alone or TNF (500 U/ml) alone developed peritonitis carcinomatosa, and died within 13 days of inoculation. These findings suggest that local combined treatment with 25-hydroxycholesterol and low-dose TNF can induce synergistic anti-tumor effects.
Authors:
S Yokoyama; F Nozawa; S Tanaka; S Muneyuki; M Ogawa
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of oncology     Volume:  16     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2000 May 
Date Detail:
Created Date:  2000-05-22     Completed Date:  2000-05-22     Revised Date:  2006-04-24    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  GREECE    
Other Details:
Languages:  eng     Pagination:  1029-33     Citation Subset:  IM    
Affiliation:
Department of Surgery II, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Carcinoma, Hepatocellular / prevention & control*
Hydroxycholesterols / administration & dosage*
Liver Neoplasms / prevention & control*
Male
Neoplasm Transplantation
Rats
Recombinant Proteins / administration & dosage*
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha / administration & dosage*
Chemical
Reg. No./Substance:
0/Hydroxycholesterols; 0/Recombinant Proteins; 0/Tumor Necrosis Factor-alpha; 2140-46-7/25-hydroxycholesterol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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