Document Detail

Combination therapy of human pancreatic cancer implanted in nude mice by oral fluoropyrimidine anticancer agent (S-1) with interferon-alpha.
MedLine Citation:
PMID:  16699793     Owner:  NLM     Status:  MEDLINE    
PURPOSE: We evaluated the antitumor and antiangiogenic activities of human natural interferon-alpha (IFN-alpha) alone or in combination with S-1 against human pancreatic cancer cells. METHODS: Three days after the subcutaneous (s.c.) implantation of tumor cells, mice (n = 12) were received s.c. injection with IFN-alpha alone (10,000 U six times a week), oral administration with S-1 alone (8 mg/kg six times a week), or both with IFN-alpha and S-1 (8, 10, 12 mg/kg six times a week). RESULTS: Administration of IFN-alpha in combination with S-1 significantly decreased progressive growth and angiogenesis of human pancreatic cancer cells. The combination therapy produced more significant inhibition in expression of the representative proangiogenic molecules, vascular endothelial growth factor and basic fibroblast growth factor than individual treatment either IFN-alpha or S-1 alone did. These treatments also decreased the staining of proliferating cell nuclear antigen, induced apoptosis and decreased microvessel density. In order to better understand the precise molecular mechanisms by which IFN-alpha and S-1 exert its effects, we have utilized cDNA microarray including 124 known genes to determine the gene expression profile altered by IFN-alpha and S-1 treatment. We found a total of seven genes which showed a twofold change after IFN-alpha and S-1 treatment in addition to VEGF, bFGF, CD31, MMP-2, MMP-7 and MMP-9. Among these genes, we found down-regulation of six genes and up-regulation of one gene, which are related to angiogenesis, tumor cell invasion and metastasis. CONCLUSIONS: These data suggest that administration of IFN-alpha in combination with S-1 may provide a novel and effective approach to the treatment of human pancreatic cancer.
Kotaro Miyake; Kunihiro Tsuchida; Hiromu Sugino; Satoru Imura; Yuji Morine; Masahiko Fujii; Mitsuo Shimada
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-05-13
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  59     ISSN:  0344-5704     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-11-22     Completed Date:  2007-01-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  113-26     Citation Subset:  IM    
Department of Digestive and Pediatric Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
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MeSH Terms
Angiogenesis Inhibitors / administration & dosage
Antibiotics, Antineoplastic / administration & dosage
Antigens, CD31 / biosynthesis
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
DNA, Complementary / biosynthesis,  genetics
Dihydrouracil Dehydrogenase (NADP) / metabolism
Fibroblast Growth Factor 2 / biosynthesis
In Situ Nick-End Labeling
Interferon-alpha / administration & dosage
Matrix Metalloproteinases / biosynthesis
Mice, Nude
Neoplasm Transplantation
Oligonucleotide Array Sequence Analysis
Pancreatic Neoplasms / drug therapy*,  pathology
Proliferating Cell Nuclear Antigen / biosynthesis
Survival Analysis
Tegafur / administration & dosage
Vascular Endothelial Growth Factor A / biosynthesis
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Antibiotics, Antineoplastic; 0/Antigens, CD31; 0/DNA, Complementary; 0/Interferon-alpha; 0/Proliferating Cell Nuclear Antigen; 0/Vascular Endothelial Growth Factor A; 103107-01-3/Fibroblast Growth Factor 2; 17902-23-7/Tegafur; EC Dehydrogenase (NADP); EC 3.4.24.-/Matrix Metalloproteinases

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